Managing menopause Jo Pollott GPR 12/09/07 Outline Menopause

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Managing menopause

• Jo Pollott
• GPR
• 12/09/07

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Outline

• Menopause
• Treatment
• Counselling
• Recent studies
• Cases

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Menopause

• Menopause
• Perimenopause
• Mean age of onset UK (natural)
• Median onset of perimenopause
• Early menopause
• Premature menopause
• Postmenopausal

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Menopause

• Menopause end of last menstrual period
• Perimenopause from the beginning of menopausal
  symptoms to the postmenopause
• Mean age of onset UK (natural) 50 yrs 9 mths
• Median onset of perimenopause 45.5 47.5 yrs
• Early menopause lt45yrs
• Premature menopause lt40yrs
• Postmenopausal 1 year after last menstrual
  period

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Aetiology

• ovaries spontaneously fail to produce oestrogen
  and progesterone usually when they have few
  remaining egg cells ? ovaries less able to
  respond to the pituitary hormones, FSH LH ?less
  oestrogen produced ? rise in FSH LH
• ovaries fail due to specific treatment such as
  chemotherapy or radiotherapy
• ovaries removed, either at time of hysterectomy
  or BSO

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Menopause Symptoms
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Menopause Symptoms

• Physical
• Menstrual irregularity
• Hot flushes
• Night sweats
• Palpitations
• Insomnia
• Joint aches
• Headaches
• Urinary symptoms
• Hair thinning
• Osteoporosis

• Psychological
• mood swings
• Irritability
• Anxiety
• difficulty concentrating
• difficulty coping
• forgetfulness
• Sexual
• Loss of libido
• Vaginal dryness /atrophy

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Diagnosing menopause 1

• Late 40s/early 50s absence of periods or
  infrequent periods along with symptoms such as
  flushes and sweats - blood or urine tests
  unnecessary.
• Measurements useful
• premature menopause is suspected
• following hysterectomy with conservation of
  ovaries (no period pattern to observe)
• unusual symptoms are present
• fertility appears to be reduced

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Diagnosing menopause 2

• blood sample d3-5 of period
• normal level does not exclude early menopausal
  transition and a raised level does not exclude
  continuing ovarian function
• Causes of temporarily raised FSH level
• stopping COCP or depot progestogens
• breast feeding
• medicines eg SSRIs

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Management .

• Cases

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Case 1

• Mrs Smith, a 49 year old non-smoking housewife
  who had a hysterectomy one year ago (ovaries
  still present), comes to discuss her hot flushes
  and night sweats with you. She is otherwise fit
  and well with no significant past medical history.

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Case 2

• Miss Green, a 51 year old sales assistant, has
  tried several combined HRT preparations over the
  last year but finds she suffers with low mood and
  breast tenderness but has good control of her hot
  flushes. She would like to discuss alternatives.

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Case 3

• Mrs Streeter, a 59 year old air stewardess who is
  4 years post-menopausal is suffering from low
  libido. She feels this is currently unacceptable
  and wants to know if you can help.

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Case 4

• Mrs Lucker is a 53 year old social worker. She
  does not want to take HRT as she has heard about
  the increased risk of breast cancer but would
  like to discuss alternative treatments for her
  menopausal symptoms. How would you advise her?

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Management lifestyle measures

• reducing/stopping smoking
• reducing alcohol intake
• reducing caffeine intake
• reducing stress
• eating healthily
• regular exercise

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Management HRT

• Oral first-choice, cost-effective
• Transdermal (patch/gel)- indications
• Patient preference
• Poor symptom control with oral treatment
• Side effects e.g. nausea with oral treatment
• History of, or risk of venous VTE (when HRT
  should only be considered after full discussion
  and appropriate investigation)
• Variable hypertension (blood pressure should be
  controlled before starting HRT)
• Hypertriglyceridaemia
• Current hepatic enzyme inducing agent, e.g.
  anticonvulsant therapy
• Bowel disorder which may affect absorption of
  oral therapy
• History of migraine (when steadier hormone levels
  may be beneficial)
• Lactose sensitivity
• History of gallstones

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HRT what to prescribe

• Post-hysterectomy (i.e. oestrogen only required)
• Low dose oral oestrogen eg Elleste solo 1mg,
  Progynova 1mg
• Low dose patch eg Estraderm MX
• Gel eg Oestrogel, Sandrena
• Oestradiol implants (last resort)

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• Perimenopausal (i.e. some continuing ovarian
  function so need daily oestrogen cyclical
  progestogen)
• Low dose tablets eg Elleste duet 1mg (estradiol
  1mg norethisterone 1mg for 12 days/28)
• Patches
• Oestrogen only Mirena IUD

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• Postmenopausal allows period free therapy
  using continuous combined therapy
• Oral e.g. Kliovance (1mg oestradiol 0.5 mgs
  norethisterone daily)
• Transdermal
• Tiblone (Livial)
• gonadomimetic synthetic preparation with weak
  oestrogenic, progestogenic androgenic
  properties
• particularly helpful for postmenopausal patients
  with reduced libido
• does not increase mammographic breast density
• long term use of Livial is thought to be
  associated with a similar increased risk of
  breast cancer to that of oestrogen alone, which
  is less than that of oestrogen plus progestogen.

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• Testosterone replacement - indicated for women
  with hypoactive sexual desire disorder (reduced
  libido) who have had hysterectomy and ovaries
  removed, and are taking oestrogen therapy.
• Intrinsa 300mcg/24hours twice weekly patch
• Testosterone implant 6 monthly

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Non-HRT Rx for Vasomotor Symptoms

• Clonidine
• Centrally active alpha-2 adrenergic agonist
• Shown to reduce hot flushes in some, but not all
  trials
• If used as first line treatment dose 50 75
  mcg twice daily
• Side effects include difficulty in sleeping, dry
  mouth, dizziness, constipation and sedation
• Interaction may occur with anti-hypertensives

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• Selective Serotonin Reuptake Inhibitors -
  believed that a variety of chemical reactions
  involving serotonin, noradrenalin and dopamine
  instrumental in initiation of the flush
• Venlafaxine - usual starting dose is 37.5mg daily
  with gradual increase in dose to reduce risk of
  side effects, which include mouth dryness,
  dizziness, insomnia, agitation and confusion
• Paroxitene, 12.5-25mg daily, has been shown to
  produce a 50 reduction in flushes
• Fluoxitene, 20mg daily has also been reported as
  producing 60 reduction
• Interactions common to these SSRIs may occur with
  MAOIs, CNS active drugs and warfarin.

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• Progestogens
• Gabapentin
• Progestogen cream
• BUTonly prescribed therapies that are licensed
  treatments for vasomotor symptoms HRT and
  clonidine

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Local treatments

• Local oestrogen can be used for vaginal and
  bladder symptoms, when systemic treatment is not
  desired or appropriate
• Oestrogen creams, pessaries and tablets - initial
  dose is nightly for 2 weeks, followed by twice
  weekly applications for maintenance
• Vaginal ring - should be replaced every 3 months
• Replens (non-hormonal vaginal moisturiser) 1
  application 3 times weekly in the morning

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Alternative therapies

• Agnus Castus
• Black Cohosh
• Dong Quai
• Evening Primrose Oil
• Gingko Biloba
• High Dose Vit E
• Red Clover
• Sage
• St Johns Wort
• RCOG Guideline
• http//www.rcog.org.uk/index.asp?PageID1561

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Bone protection

• HRT should not be used as first-line just for
  prevention of osteoporosis
• SERMS (Selective Oestrogen Receptor Modulators)
  i.e. Raloxifene -
• Indicated for post menopausal women at risk of or
  with existing osteoporosis and who are unwilling
  or unable to take HRT
• Do not control vasomotor symptoms

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• Bisphosphonates
• Currently used as first-line treatments in
  postmenopausal women with proven osteoporosis not
  suffering from menopausal symptoms
• Strontium Ranelate
• Dual action - prevents bone loss increases bone
  formation
• Significantly reduces the risk of vertebral and
  hip fracture
• Well tolerated
• Suitable for first line use for the treatment of
  osteoporosis - ?prescribable by GPs

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• Calcium and Vitamin D supplements
• Can be used to prevent bone loss when dietary
  intake is low
• Should be given in addition to osteoporosis
  treatment if aged gt70 or if aged lt70 and dietary
  insufficient.
• Parathyroid hormone
• Calcitonin

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www.menopausematters.co.uk
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Starting HRT.

• What should you discuss with patients?
• What are the contraindications to HRT?

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Counselling 1

• Contraindications for HRT
• Pregnancy
• Undiagnosed abnormal vaginal bleeding
• Active thromboembolic disorder or acute-phase
  myocardial infarction
• Suspected or active breast or endometrial cancer
• Active liver disease with abnormal liver function
  tests
• Porphyria cutanea tarda

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Counselling 2

• Risks of HRT
• Breast cancer with long-term treatment (gt 5
  years) approx 1.5 extra cases/1000 women aged
  50 -64yrs (tibolone slightly lower increase)
• VTE 1 extra case/1000 women aged 50-59yrs with
  oestrogen only, 4 extra cases with combined HRT
  used for 5 years NB predisposing risk factors
  should be considered as risks may outweigh
  benefits
• Stroke 2 extra cases/1000 in women using
  oestrogen only, 1 extra case/1000 women using
  combined HRT aged 50-59yrs over 5 yrs
• Endometrial cancer increased risk with
  oestrogen only (5 extra cases/1000) risk
  reduced by adding progestogen
• Ovarian cancer 1 extra case/1000 using
  oestrogen-only (figures for combined HRT unknown)
• HRT not indicated for cardiovascular benefit -
  should only be prescribed to women who have, or
  are at risk of cardiovascular disease if there
  are good indications, and after full discussion

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Counselling - 3

• HRT not contraceptive
• Woman considered fertile until 2 yrs after LMP if
  lt50yrs, 1yr if gt50yrs
• lt50yrs can use low-oestrogen COCP but stop at
  50yrs
• Surgery
• HRT should be stopped 4-6 wks prior to major
  surgery under GA
• If not stopped prophylactic LMWH TEDS advised

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Counselling - 4

• Immediately stop HRT if
• Sudden severe chest pain
• Sudden breathlessness
• Unexplained unilateral severe pain in calf
• Serious neurological effects
• Hepatitis, jaundice, hepatomegaly
• BP gt160mmHg systolic, or 100mmHg diastolic
• Prolonged immobility
• Detection of risk factor contraindicating
  treatment

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When to refer

• Persistent side-effects following logical therapy
  changes
• Poor symptom control
• Bleeding problems
• Sequential therapy - change in pattern of
  bleeding including increased duration, frequency
  and/or heaviness, and irregular bleeding.
• Continuous combined therapy or tibolone - if
  still bleeding after 6 months of therapy or if
  bleeding occurs after a spell of amenorrhoea.
• SERMS - any bleeding whilst on therapy should be
  treated as PMB
• Complex medical history
• Past hx of hormone dependent cancer
• Patient request

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Womens Health Initiative

• 2 parallel multicentre, randomised, double blind,
  placebo controlled studies
• Evaluated risks/benefits og oestrogen alone and
  in combination with progesterone in healthy
  postmenopausal women
• 16,608 postmenopausal women with intact uterus
  further post-hysterectomy arm of 10,739 women
  aged 50-79yrs from Sept 1993 July 2002
• Found HRT
• Does not confer CVS or cognitive protection
• Increases risk of breast ca in women with a
  uterus
• Increases risk of VTE
• Does not improve overall quality of life
• Reduced fracture rates
• Reduces vasomotor symptoms
• Limitations
• Looked at postmenopausal women so ?applicability
  to early menopause
• Average age of starting Rx was 63 yrs (HRT
  normally used in women aged 45-55yrs)
• High dose oestrogens used in trial

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Million Women Study

• National study of women's health, involving more
  than one million UK women aged 50 and over
• Collaborative project between Cancer Research UK
  and the National Health Service Breast Screening
  Programme, with additional funding from the
  Medical Research Council
• Breast cancer and HRT in the Million Women Study
  (Lancet 2003 362(9382)419-27)
• Observational study
• 1,084,110 women living in UK
• Found current users of HRT more likely to develop
  breast ca (relative risk 1.66) and die from it
  (RR 1.22)
• Past users not at increased risk
• Little variation between strength/type of HRT

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WISDOM (Womens International Study of long
Duration Oestrogen after Menopause)

• Multi-centre randomised controlled trial of HRT
  in postmenopausal women
• Confirms that HRT should not be prescribed to
  older women who are many years past menopause to
  help prevent chronic conditions such as heart
  disease
• Supports view that HRT is a safe short term
  treatment for younger women in early menopause to
  relieve symptoms and improve quality of life
• Supports window of opportunity theory
• BMJ, doi10.1136/bmj.39266.425069.AD (published
  11 July 2007)

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Useful resources

• www.menopausematters.co.uk
• http//www.millionwomenstudy.org/
• http//www.nhlbi.nih.gov/whi/
• www.clinicalevidence.bmj.com