Transcript Shoulder Difficulty

Max Brinsmead PhD FRANZCOG
June 2015
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Menopause is technically a woman’s last
menstrual period
 That is the end of potential reproductive life when
follicular activity in the ovaries cease and oestrogen
levels fall
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Often preceded by several years of erratic
cycling. This is called the climacteric...
 A rather confusing term
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For practical purposes a woman is said to be
post menopausal when she has not had a
menstrual period for 12 months (and other
causes of secondary amenorrhoea have been excluded)
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Essentially a diagnosis in retrospect
Is best made on clinical grounds
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Age 40 – 60
Amenorrhoea
Hot flushes
Other causes of amenorrhoea excluded
In fact, women drift in and out of a state of
ovarian failure, often over a period of 5 – 10
years...
▪ And this is why measures of FSH and E2 are
unreliable
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The effects of oestrogen deficiency
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Hot flushes
Genital tract atrophy
Accelerated bone mineral loss
Changed fat distribution
Skin, hair and dentition effects
?Acceleration of atherosclerosis
?Cognitive and mood changes
?Reduced libido
The pros and cons of hormone replacement
therapy (HRT)
 Premature menopause
 Postmenopausal bleeding
 The effect of Tamoxifen on the Endometrium
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Sensation of heat with sweating and palpitations
▪ Can be documented by measuring skin temperature
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Last 2 – 30 minutes
▪ Frequency quite variable
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May effect just the face and head or the whole body
Night sweats and insomnia the worst aspect
Occur in 85% of women
▪ But only 15% so severe as to demand treatment
▪ Tend to decrease with time
▪ But can persist for years in a few women
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Known triggers include:
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Heat
Emotion
Alcohol, Caffeine, Smoking
Spicy foods
Correlate in time with GnRH release but exact
mechanism unknown
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Education
▪ Cultural expectations seem important
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Non pharmacological
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Avoid known triggers
Exercise no benefit on RCT
Meditation/Relaxation of benefit in 1:2 RCT’s
Acupuncture, homeopathy, Vitamin E, Magnetic devices not
effective
Pharmacological
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ERT & HRT highly effective on RCT
Tibilone
SSRI and SNRI (Selective Serotonin Re-uptake Inhibitors)
Clonidine
Gabapentin
Soy products and Phytoestrogens inconclusive
Black cohosh effective in 66% women but safety for long
term use uncertain
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Background
▪ From 1960 – 1990 a number of observational studies
suggested that postmenopausal hormone use (HRT) reduced
the risk of cardiovascular disease
▪ Taken together with the burden of illness from osteoporosis
in older women, HRT was widely prescribed prophylactically
to prevent these two diseases
▪ Vigorously supported by drug firms and many women who
saw this as an “elixir of youth”
▪ In 2002 the results of a large prospective RCT in the US
examined the risks and benefits of HRT in postmenopausal
women
▪ It is called the Women’s Health Initiative (WHI) and it caused
waves around the world
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Recruited 64,500 women for study over 15 years with the aim to
evaluate risks and benefits of a low fat diet, HRT and calcium
supplements
One part of that study was STOPPED after 5.2 years because of
an increased risk of breast cancer
There was also an increased risk of cardiovascular disease in this
group
Thus negating the principal argument for prophylactic HRT
This RCT involved 16608 women aged 50-79 years with an intact
uterus at baseline in 40 US centres over 1993-98
Combined HRT (Equine oestrogen 0.625 mg plus Provera 2.5 mg)
was compared to placebo
Outcomes studied included thromboembolism, stroke, heart
attack, breast, uterine and colon cancer and hip fracture
Results were published as risk ratios (95% confidence limits) and
as absolute risk per 10,000 women
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Breast Cancer
 RR = 1.26 (CI 1.00 – 1.59)
 8 more cases per 10,000 women years
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Cardiovascular Disease
 RR = 1.29 (CI 1.02 – 1.63)
 7 more cases per 10,000 women years
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Stroke
 RR = 1.41 (CI 1.07 – 1.85)
 7 more events per 10,000 women years
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Pulmonary Embolus
 RR = 2.13 (CI 1.39 – 3.25)
 8 more cases per 10,000 women years
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Colorectal Cancer
 RR = 0.63 (CI 0.43 – 0.92)
 6 fewer cases per 10,000 women years
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Hip Fractures
 RR = 0.66 (CI 0.45 – 0.98)
 4 fewer cases per 10,000 women years
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Endometrial Cancer
 RR = 0.83 (CI 0.47 – 1.47)
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All Mortality RR = 0.98 (CI 0.82 – 1.18)
 That is unchanged
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The study did not evaluate any aspect of patient
satisfaction or quality of life
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Another arm of the study that involved 10, 739
women after hysterectomy who received
oestrogen-only HRT. Published in 2004
 Confirmed an increased risk of stroke but not cardiovascular
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disease or thromboembolism
A reduced risk of hip fracture but no effect on colon cancer
A trend towards reduced risk of breast cancer!
This study found no effect from ERT on a number of measures
of quality of life
Including cognitive functioning and dementia
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Many criticisms of the study made
 Some are statistical
 Some focus on “horse oestrogens” and the progestin used
 All point to the fact that ORAL oestrogens have profound effects on
the liver
 Most point out that many of the participants were long past
menopausal and “too old” to benefit
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Efforts to produce a selective oestrogen analogue
without breast effects resulted in...
 “Evista” = Raloxifene
 “Livial” = Tibilone
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HRT use in Australia and the US fell by 40%
 And the incidence of postmenopausal breast cancer fell by 7%
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But nobody seriously argues that all women should take
HRT forever
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Because the carcinogenic potential for HRT on the breast
does not appear for at least 5 years...
 Combined HRT for the relief of menopausal symptoms is
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appropriate for a woman with a uterus in the minimum doses
and for the minimum period required
Continuing HRT beyond this is a matter for individuals & their
doctors and proceeds on the basis of “informed consensus”
Patients at risk of thromboembolism should be treated with
special care
Patients with a history of breast cancer are best treated with
non-hormonal alternatives
There are better alternatives for the prevention and treatment
of osteoporosis (Biphosphonates & Vitamin D)
Patients without a uterus can use oestrogen-only ERT with
greater impunity
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Do not use continuous combined preparations until age >55
years
 Use sequential preparations and warn about withdrawal bleeding
 These preparations are NOT contraceptive
 And irregular bleeding is often due to spontaneous ovarian activity
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Warn the patient about side effects including...
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Mastalgia
PV bleeding
Dysphoria
Thrush
Non oral routes are preferred but expensive
 Consider vaginal use of tablets that are not enteric coated
 Remember the use of Mirena as a good method of progestin
administration
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Wean patients off HRT very slowly over weeks
 Rebound hot flushes can be quite severe
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HRT for Hot Flushes
 24 trials, 3329 women studied
 Oestrogen only (ERT) or oestrogen plus progestin (HRT) are
highly effective in preventing hot flushes
 Side effects include PV bleeding, mastalgia and dysphoria
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Minimum Doses of Progestin with HRT required to
avoid Endometrial Hyperplasia
 45 studies
 All doses of ERT results in endometrial hyperplasia after 12m
 Counteracted by not less than 1.0 mg Norethisterone or 1.5 mg
Medroxyprogesterone daily
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Alternatives to HRT for Women with Breast Cancer
 16 RCT’s of agent against placebo
 Clonidine, SSRI, SNRI, Gabapentin and relaxation therapy all
mildly effective
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HRT and ERT for Cognitive Function in Postmenopausal
Women
 24 trials 10,114 women
 Neither ERT nor HRT prevents cognitive impairment with age
 After 1 year of ERT or 3 years of HRT the net effect is
NEGATIVE i.e. Worse cognitive function
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Exercise and Hot Flushes
 No convincing effect
 But one study found that exercise enhanced the ameliorating
effects of soy products
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Vaginal Oestrogen Use
 19 trials 4162 women
 Creams, pessaries and tablets all highly successful in treating
the symptoms of vaginal atrophy
 But vaginal rings that release oestrogen are the best
 14trials examined safety and some showed evidence for
vaginal bleeding, mastalgia, perineal pain and endometrial
hyperplasia
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HRT for Urinary Incontinence in Postmenopausal
Women
 33 trials 19,313 women
 Systematic oestrogen or oestrogen plus progestin makes
urinary incontinence significantly WORSE
 Local (PV) oestrogen has a mildly beneficial effect
 Mostly by reducing urinary frequency
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Definition
▪ Menopause before the age of 40
▪ 45 by some criteria
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Diagnosis
▪ Amenorrhoea with high FSH
▪ Beware of resistant ovary syndrome...
▪ A condition of great unpredictability
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Causes
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Chromosomal
Chemotherapy or Radiotherapy
Surgical
There is a familial component (gene identified)
May be auto immune
Smoking
Hysterectomy even with preservation of the ovaries
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Because of the association between bone mass, age of
menopause and osteoporosis there is a general consensus
that premature menopause requires treatment at least until
the mid 50’s
Also required when symptomatic
If there is a uterus present then combined HRT in greater
doses than the average is usually required
E2 by implant and a Mirena is a good option
Oestrogen only (ERT) required after hysterectomy
Management of patients who have oestrogen-dependent
tumours or residual pelvic endometriosis poses real problems
Donor eggs are an option for infertility
Should be regarded as due to Ca of the endometrium
until proven otherwise
 In fact, only 1:10 is Ca endometrium an the rest are due to
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Beware of the high risk patient
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Polyps
Atrophic “vaginitis”
Patient not truly menopausal
Administered hormones
Obese, diabetic and often hypertensive
Infertility (role of PCO disorder controversial)
Unopposed oestrogen therapy or Tamoxifen
Late menopause
Ca of breast or colon etc.
Make sure that the bleeding is vaginal in origin – not
bowel or bladder
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Examination during bleeding is desirable
 To confirm the symptom & ascertain site
 Take an endocervical smear for cytology
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Ultrasound of the uterus has a role
 Will exclude Ca endometrium with 95 – 98% sensitivity if an
endometrial stripe of ≤ 4mm is seen
 The commonest cause of endometrial widening is polyps
 They are best delineated by saline utrasonography
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Pipelle endometrial biopsy will diagnose up to 99% of Ca
endometrium
 But is often negative or nondiagnostic in cases of polyp
 May require gentle cervical dilatation
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Hysteroscopy & Biopsy is the gold standard
 But may be omitted in selected cases
 Can be done as an outpatient procedure
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Vaginal oestrogen and observation for suspected atrophic vaginitis is
an option
This drug is widely used after breast cancer surgery
But within 12m of use 75% of patients will have endometrial
changes on ultrasound
 These consist of microcystic change in the proximal
endometrium and adjacent myometrium
 Postmenopausal patients on Tamoxifen are at small risk of
developing endometrial cancer
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 Risk is between 0.2 and 4% per year
 And it will always present with PV bleeding
Routine ultrasound monitoring of the endometrium is
not recommended
 And ultrasound has a limited role in the investigation of
these patients if they experience bleeding
 Early recourse to hysteroscopy and biopsy is best
 But Pipelle may also have role
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