Menopause Matters

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Menopause Matters!

• Dr Heather Currie

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Plan!

• Menopausewhat its all about!
• Consequences of menopause
• Management

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Definitions

• Menopause
• Premenopause
• Perimenopause
• Climacteric
• Postmenopause

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Demographics

• 1850
• Age of menopause - 45 yrs.
• Life expectancy - 45 yrs.
• 2008
• Age of menopause - 52 yrs.
• Life expectancy - 82 yrs.
• Today gt 30 life postmenopausal

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Worldwide

• 1990, 476 million postmenopausal women
• 2030, 1200 million postmenopausal women

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Influences on age of menopause

• Genetics
• Biologicalage menarche, menstrual cycle length,
  OCP, parity
• Diet and lifestylenutrition, smoking, alcohol
• Education

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Physiology
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Oocytes

• 5th month gestation7 million
• Birth1-2 million
• Puberty400,000
• 40--rapid decline!

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Types of menopause

• Spontaneous
• Surgical
• Drug induced

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Premature ovarian failure

• Menopause lt age 40
• Idiopathic
• Familial
• Autoimmune
• Chromosomal
• Exclude correctable causes

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Premature ovarian failure

• Special considerations
• Symptom control
• Bone health
• Cardiovascular health
• Dementia
• Fertility

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Diagnosis of menopause

• Blood test?
• Urine test?

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Early Symptoms

• Periods changing
• Vasomotor
• Insomnia
• Mood
• Connective tissue
• Cognitive function
• Coping

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Vasomotor symptoms
Source Adapted from Freedman, RR. Seminars in
Reproductive Medicine 2005 23 (2) 117-125
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Influences on impact of symptoms

• Diet and lifestylePhytoestrogens, smoking,
  alcohol, caffeine, BMI, exercise
• Cultures, attitudes, taboos
• Translations
• Negative life events
• Climate
• Treatment requirements

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Intermediate symptoms

• Urogenital atrophy
• Vagina and bladder
• Hugely under-reported and under-treated

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Timing

• Perimenopausally
• Shortly post menopause
• 5 10 years post menopause
• Some situations premenopausally

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Diagnosis

• History and examination
• ? pH testing
• Vaginal health indexfrom Bachmann GA.
  Vulvo-vaginal complaints. In Lobo R, editor,
  Treatment of the post-menopausal woman. New York
  Raven Press 1994.

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Vaginal health index
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Symptoms of vaginal atrophy

• Reduced lubrication
• Dryness
• Discomfort during intercourse
• Decreased frequency of intercourse
• Vaginal and vulval irritation
• Discharge
• Bleeding
• Relationship problems

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Lower urinary tract atrophy

• Estrogen receptors in bladder trigone, detrusor
  muscle, urethral sphincter
• Deficiency leads to dysuria, frequency, urgency,
  urge incontinence, nocturia

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Pelvic floor atrophy

• Estrogen deficiency leads to changes in collagen
  in pelvic floor
• Bulging of vaginal walls
• Descent of cervix
• Dragging sensation
• Shortened urethra
• UTIs and stress incontinence

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Incidence

• 15 premenopausal women
• 10 40 postmenopausal
• 10 25 women taking systemic HRT
• 2/3 by age 75

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Online survey incidence

• 1002 respondents
• 54 perimenopausal
• 63 menopausal
• 43 sexual relationship affected by symptoms
• 42 made excuses
• 60 less confident
• 49 bladder symptoms

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Under reporting

• 20 25 with symptoms seek help
• Online survey
• Despite 88 feeling active sex life important,
  only
• 20 discussed symptoms with health professional,
• 61 hide symptoms from partner
• Bladder symptoms
• only 21 discussed with health professional

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Current Management
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Vaginal dryness
Menopause matters survey 1,300 responses
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Possible reasons

• Embarrassment
• Not seen as serious illness
• Lack of time
• Health professionals attitude
• Unaware of availability of treatments
• Not wanting to feel old

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Long term health

• Osteoporosis
• Cardiovascular disease
• Dementia
• Breast cancer

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Death from CVD

• Mr Mrs Smith!
• Europe, stats from 2005
• 43 of men
• 57 of women

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CVD in women
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Causes of death in European women
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Womens perceptions of their greatest health
problems
Cardiovascular disease
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Dont know/ no answer
Breast cancer
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Other problems
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Cancer
Mosca et al. Arch Fam Med 2000.
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Incidence of CVD Relation to Menopause Status
The Framingham Study
Incidence (per 1000 women)
Age (years)
n 2873. Kannel WB, et al. Ann Intern Med.
197685447-52.
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Effect of estrogen lack

• Change in BMI, fat distribution
• Inc LDL cholesterol
• Decreased HDL
• Increase TGs
• Blood pressure
• Glucose/insulin metabolism
• 4 fold increased risk CVD
• Prem menopause53 inc risk CHD

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Symptoms of CVD in women

• Different from those in men
• Angina can be mistaken for indigestion or
  heartburn
• MI symptoms can include overwhelming fatigue,
  shortness of breath, nausea, or indigestion

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Other problems

• Often present late
• Other medical problems
• Poorly represented in trials
• Less interventions
• Worse prognosis following MI
• 38 women die in 1 year, 25 men
• In 6 years, further MI in 35 women, 18 men

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Contributory factors
Obese population aged 15 and above

• Weight
• Dietary
• Exercise
• Smoking

OECD Factbook 2005 www.sourceoecd.org/factbook
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So

• Menopause is a big deal!
• Holistic approach
• Assess symptoms and impact
• Contributory factors
• Long term health
• Inform
• Aid decision making

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Management

• Does every woman need to be managed?
• Explanation
• Diet and lifestyle advice
• HRT
• Alternatives

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HRT

• Huge change in prescribing
• Loss of confidence
• Where are we now?
• Indications symptom control and prevention of
  osteoporosis

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WHI trial

• 16,608 HEALTHY postmenopausal women, aged 50-79,
  intact uterus
• Randomised to HRT versus placebo
• Hysterectomised-estrogen only (gt10,000 women)
• Combined HRT arm stopped after 5 years
• Estrogen only stopped after 7 years

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WHI combined HRT results
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Further analysis

• Increase in breast cancer only in women who took
  HRT before the trial
• Only women 20 or more years postmenopause had
  statistically increased risk CHD
• Increased risk CHD was only in 1st year with
  decrease thereafter. No overall increase.

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Estrogen only

• No increased risk breast cancer
• No increase CHD
• Similar increase stroke to combined HRT
• All VTEs 0.69 per 1,000 women per year

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Final analysis-JAMA

• Women aged 50-59
• Minimal risks
• Likely significant benefits
• Lower risk CVD, lower risk death, no increased
  risk stroke, breast canceronly increased if HRT
  taken before

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Does the timing of HRT matter?

• Meta-analysis of 23 trials
• 39,049 participants
• Odds ratio for CHD differed with age at enrolment
• Under 60 - 0.6832 reduction (significant)
• Over 60 - 1.03

Salpeter et al J Gen Int Med 200419791-804
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Timing of HRT for mortality

• Meta-analysis of 30 trials
• 27,000 participants
• Odds ratio for mortality differed with age at
  enrolment
• Under 60 - 0.61significant 39 reduction
• Over 60 - 1.03
• Nurses Health Study HRT within 2 years of LMP
  - 0.63

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Effect of Hormone Therapy on Atherosclerosis
Varies With Stage of Reproductive Life
Premenopause
Perimenopause
Postmenopause
5
15
35-45 yrs
45-55 yrs
55-65 yrs
65 yrs
25-35 yrs
15-25 yrs
Primary Benefits of HT
No Benefits of HT
Benefits of Endogenous E2
Mikkola TS, et al. Ann Med. 200436402-13.
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The Effect of Body Mass on the Risk of CHD
Putting the WHI Results in Perspective
RH relative hazard. Mean BMI 28.5 kg/m2. BMI
data from Willett WC, et al. JAMA.
1995273461-5. WHI data from Manson JE, et al. N
Engl J Med. 2003349523-34.
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CHD PRIMARY PREVENTION
CHD

• low-dose aspirin reduces CVA risk
• no reduction in CHD risk with low-dose aspirin
• no reduction in CHD mortality with statins
• reduction in CHD risk with HRT

Hodis and Mack. Menopause 2007 14 1-14
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BENEFITS AND RISKS WOMEN
CHD
breast cancer
Hodis and Mack. Menopause 2007 14 1-14
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SummaryHRT and CHD

• Window of opportunity
• Best if started within 6 years of menopause
  and/or before age 60
• Increased benefit with longer use
• Use for at least 5 years
• Results of further studies on timing, types and
  routes awaited
• Similar risks to other commonly used drugs

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HRT VTE meta-analysis

• Oral estrogen OR 2.5 obs, 2.1 rct
• 1st year4.0, gt 1year2.1
• No sig. difference opposed or unopposed
• Transdermalno increase
• Oral estrogen? prothrombin fragment 12, ?
  antithrombin, acquired resistance to activated
  protein C
• Transdermalno effect

Canonico et al BMJ 20083361227-1231
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Ischaemic Stroke--WHI

• Overall combined HRT- 0.85/1,000/year
• ---Only appreciable in 70-79 age group-extra 1.3
  per 1,000 per year
• Overall estrogen only- 1.19/1,000/year
• ---Only appreciable in 60-69 age group-extra 1.9
  per 1,000 per year
  
• And in 70-79 age group-extra 1.4 per 1,000 per
  year

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Hypertension and Risk of StrokeDanish Nurse Study
Lokkegaard et al Arch Neurol 2003601379
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Estrogen and Stroke a case for low-dose estrogen

• Low doses may confer protection while higher
  doses may increase risk
• Risks may be lower with transdermal
• Thrombogenic effects
• C-reactive Protein

Birge ss Menopause 200613(5)719-20
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WHI CEE/MPA Study Incidence of Diabetes
Placebo
HR 0.79 95 CI 0.670.93
Incidence
CEE/MPA
Time (years)
Margolis KL, et al. Diabetologia. 2004471175-87.
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HRT and Breast cancer

• Estrogen onlydecreased risk at 7 years of 8 per
  10,000 women per year
• Combined HRTsignificant after 7 years with
  increase thereafter of 8 per 10,000 per year
• Possibly affected by route and type of progestogen

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Breast cancer risk

• Cumulated data per 10,000 women per yr
• Oral cc HRT 8.0 to 12
• Statin therapy -10 to 77
• (Statin therapy 22 GI cancer)

Hodis and Mack. Menopause 2007 14 1-14
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IMS report May 2008

• HRT initiated in the early postmenopausal period
  in healthy women is safe. Like all medicines, HRT
  needs to be used appropriately but it is
  essential that women in early menopause, when
  suffering menopausal symptoms, should have the
  option of using HRT.

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Benefits v Risks

• lt50, benefitsgtgtrisks, all women should be offered
  HRT
• 50-60, benefitsgtrisks for symptomatic women
• 60-70 benefitsrisks, individualise and ?change
  to transdermal therapy
• gt70 risksgtbenefits

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Prescribing HRT

• Initial investigations
• Appropriate type
• Review
• Duration of treatment

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Review

• Starting or changing HRT3 months
• When settled - annual review
• Assess symptom control
• Presence of side effects
• BP, weight
• Review risks and benefits
• Encourage routine screening

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HRThow long?

• Symptom relief
• 3-5 years then gradual withdrawal
• Restart if symptoms recur, NO arbitrary limits
• Prevention of osteoporosis
• 5-10 years minimum?
• Premature menopause
• Treat to average age of menopause
• NB Breast cancer risk applies to gt51 yrs

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When to refer

• Persistent side effects
• Poor symptom control
• Bleeding
• Sequential
• Continuous combined
• Complex medical history
• Hormone dependant cancer
• Patient request

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Types of vaginal oestrogen
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Duration of treatment

• Problems with licensing
• Few studies on long term use
• Unlikely systemic absorption
• Symptoms frequently return on stopping treatment

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Alternatives

• Prescribed
• Clonidine
• SSRIs SSNRIs
• Gabapentin
• Progestogens
• OTC
• Techniques

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Resources

• Menopause Matters www.menopausematters.co.uk
• British Menopause Society www.thebms.org.uk
• Thank-you

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London, UK May 16 20, 2009
www.kenes.com/emas2009