menopause symptoms and quality of life · 2014-04-29 · after menopause, including, but not...
TRANSCRIPT
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Andrea R. Genazzani
Menopause symptoms and
quality of life
University of Pisa, Italy
Disclosure of Interest: Nothing to Disclose
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SEX STEROIDS INFLUENCE THE FUNCTION OF MULTIPLE TISSUES, ORGANS AND SYSTEMS. NEARLY EVERY HUMAN CELL IS SENSITIVE TO THESE HORMONES.
SEX STEROIDS IN WOMEN
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MENOPAUSE IS ABOUT THE WOMAN IN FRONT OF US
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MENOPAUSE AND A WOMAN’S BODY
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THE MAIN CHALLENGE
THE MAIN MEDICAL NEEDS
ISSUES IN MENOPAUSAL MEDICINE
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A WOMAN’S PERSONAL AND SOCIAL IDENTITY
MOTHERHOOD BEAUTY
MOTHERHOOD BEAUTY
EROTICISM CAREER
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MENOPAUSE IS ABOUT QUALITY OF LIFE
THAT IS WHAT LEARNING IS.
YOU SUDDENLY UNDERSTAND
SOMETHING YOU'VE
UNDERSTOOD ALL YOUR LIFE,
BUT IN A NEW WAY.
DORIS LESSING
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Qol after Menopause depends on:
general health, lifestyle
physical functioning and integrity
psychological/emotional stability
positive partnership (incl. sexual life)
education, professional activity
religion, cultural environment
social integration before menopause
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PROBLEMS WITH QOL ASSESSMENT
• Minimal definitional agreement
• Objective measurement difficult
• QOL often oversimplified as health status (symptom inventory vs. measure of sense of well-being)
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IMPORTANCE OF QUALITY OF LIFE MEASUREMENT
Accurate appraisal of Quality of Life:
• Critical to enhancing treatment adherence
• Enhances clinician interactions with patients
• Helps assess and optimize treatment effectiveness
• Improves overall patient satisfaction with treatment
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Qol instruments vary based on the domain investigated
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GLOBAL QOL
• A reflection of a person’s beliefs about
functioning and achieving in various
aspects of life
• A spectrum that ranges from perceived
distress at one end to the absence of
distress and a sense of well-being at the
other
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HEALTH-RELATED QOL
• The domains of physical and
psychological functioning
• The patients’ perception of their physical,
cognitive and mental health
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Fol 20-100 pg/mL Ovu 300-500 pg/mL Lut 100-300 pg/mL
10-20 pg/mL
I tr. 1.000-5.000 pg/mL II tr. 5.000-15.000 pg/mL III tr. 10.000-40.000 pg/mL
ESTROGENS DURING A WOMAN’S LIFE
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Age – healthy women
100
50
0.0 20 years 40 years
50%
reduction
DHEA
DHEAS
TESTOSTERONE
Androgens decline between 20 and 40 years
%
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Cl- channel
b
a
g
g
a
PREG(S)
General anesthetics
GABA
Benzodiazepines Imidazopyridines
Pyrazolopyrimidines
Barbiturates
Ethanol
Neurosteroids and GABA-A
Cellular excitability
Network synchronization
Synaptic plasticity
MOOD
EMOTIONAL STATE
AFFECTIVITY
ALLOPREGNANOLONE 3-DIOL
DHEA(S)
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The Brain-Steroids Aging A Multisignaling process
TIME – LIFE EVENTS
GENETIC
FACTORS DURING AGING
ENVIRONMENT
BRAIN
HORMONES
BODY Function/ Activities
AR Genazzani et al, Hum Rep Update
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SEXUAL PROBLEMS & DISTRESS IN US WOMEN
Shifren et al, 2008
0
5
10
15
20
18-44 45-64 >64 years
Desire
Arousal
Orgasm
Any
%
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HOT FLUSHES AND QOL
• Interfere with daily activities
• Impact on other members of family
• Interfere with sleep cycle
• Impair sexual function
• Result in :
– fatigue
– Loss of concentration
– Depression
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Estradiol
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DOSE RESPONSE TO ESTROGEN THERAPY Number of Moderate-Severe Hot Flushes
0
10
20
30
40
50
60
70
80 Placebo
0.25mg E
0.5mg E
1mg E
2mg E
Notelovitz et al, OG 2000, 95:726
Nu
mb
er
significantly (p < 0.05)
different from placebo
*
*
*
*
0 1 4 5 6 7 8 9 10 11 12 3
Weeks
2
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J Clin Endocrinol Metab, July 2010, 95(Suppl 1):S7–S66
RISKS AND BENEFITS OF HRT
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J Clin Endocrinol Metab, July 2010, 95(Suppl 1):S7–S66
RISKS AND BENEFITS OF HRT
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6543210-1-2-3-4-5-6
Total Number of Objective Hot Flashes during Sleeping Hours
6
5
4
3
2
1
0
-1
-2
-3
-4
-5
-6
De
laye
d P
ara
gra
ph
Rec
all
(sc
ore
ad
jus
ted
fo
r o
the
r s
ign
ific
an
t p
red
icto
rs)
6543210-1-2-3-4-5-6
Total Number of Objective Hot Flashes during Sleeping Hours
6
5
4
3
2
1
0
-1
-2
-3
-4
-5
-6
De
laye
d P
ara
gra
ph
Rec
all
(sc
ore
ad
jus
ted
fo
r o
the
r s
ign
ific
an
t p
red
icto
rs)
HF AND COGNITIVE FUNCTION
Objective hot flashes are negatively related to verbal memory performance in midlife women.
Maki P., Menopause 2008
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MENOPAUSE SYMPTOMS AND DEPRESSION
Brown et al., Maturitas 2008
OR v
s.
asym
pto
matic w
om
en
HF Irritability
5
4
3
1
2
Risk of depression
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HF ARE ASSOCIATED WITH LOWER BMD Study of Women's Health Across the Nation
2,213 participants aged 42 to 52 years; 5-year follow-up
Crandall, Carolyn J.et al., Menopause 2009
POST MEN
PERI MEN
0.01
0
0.005
BM
D (
g/c
m2)
PRE MEN
Difference in SPINE BMD (HF vs. no HF)
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HF AND CV RISK FACTORS
Gast et al., Hypertension 2008
5523 women aged 46-57 years, of whom 38 % reported night sweats and 39 % hot flashes
1.20 (1.07-1.34)
1.52 (1.25-1.84)
HTN HIGH cholesterol
1.5
1.2
0.9
0.3
0.6
OR v
s.
wom
en w
ithout
HF
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WOMEN MAY BE DIFFERENTLY VULNERABLE TO MENOPAUSAL CHANGES
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E2
VASODILATATION
INFLAMMATION
LESION PROGRESSION
E2
VASODILATATION
INFLAMMATION
PLAQUE INSTABILITY
PLAQUE THROMBOSIS
ESTROGENS AND CVD
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30 70 60 40 50 80
WHI
HERS
PHASE
NHS
secondary prevention
ERA
yr
primary prevention
CLINICAL TRIALS
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HRT: IS THERE A WINDOW OF OPPORTUNITY TO START?
CEE + MPA
YEARS SINCE MENOPAUSE
0 1.0 2.5
Hazard Ratio (95% CI)
0.5 1.5 2.0
0 1.0 2.5
Hazard Ratio (95% CI)
0.5 1.5 2.0
0.56 <10
0.92 10-19
1.04 > 20
0.89 <10
1.22 10-19
1.71 > 20
HAZARD RATIOS
CEE
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Figure 5. Cumulative Annualized Incidence Rates for Clinical Outcomes in the Women's
Health Initiative Estrogen-Alone Trial According to 10-Year Age Groups at Enrollment
LaCroix, A. Z. et al. JAMA 2011;305:1305-1314
Copyright restrictions may apply.
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WHI SUB-STUDY (CEE-ALONE) ONLY WOMEN 50-59 Y AT ENROLLMENT CT SCAN OF THE HEART – CORONARY CALCIFICATIONS MEAN CORONARY-ARTERY CALCIUM SCORE WAS LOWER AMONG WOMEN RECEIVING ESTROGEN (83.1) THAN AMONG THOSE RECEIVING PLACEBO (123.1) (P=0.02).
JA Manson et al. N Engl J Med. 2007
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Schierbeck L L et al. BMJ 2012;345:bmj.e6409
©2012 by British Medical Journal Publishing Group
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Schierbeck L L et al. BMJ 2012;345:bmj.e6409
©2012 by British Medical Journal Publishing Group
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Schierbeck L L et al. BMJ 2012;345:bmj.e6409
©2012 by British Medical Journal Publishing Group
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Primary Prevention of CHD with HRT in Clinical Perspective
*Women <60 years old and/or <10 years since menopause when randomized
1Salpeter S, et al. J Gen Intern Med 2004;19:791-804. 2Salpeter S, et al. J Gen Intern Med 2006;21:363-366. 3Walsh JME, et al. JAMA 2004;21:363-366. 4Ridker PM, et al. N Engl J Med 2005;352:1293-1304.
Hormone Lipid Outcome Therapy1,2* Lowering3 Aspirin4
CHD 0.68 (0.48-0.96) 0.89 (0.69-1.09) 0.91 (0.80-1.03)
Total Mortality 0.61 (0.39-0.95) 0.95 (0.62-1.46) 0.95 (0.85-1.06)
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Lindsay. Clin Obstet Gynecol. 1987;30:847-859.
44
42
40
38
36
34
Meta
carp
al BM
C
(m
g/m
m)
Blue area represents placebo-treated population of oophorectomized women
Years
From oophorectomy
From 3 years after oophorectomy
From 6 years after oophorectomy
0 2 4 6 8 10 12 14 16
ERT AND BONE LOSS
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Zandi PP et al, JAMA. 2002;288:2123-2129
HRT and Alzheimer’s Disease
The Cache County Study
65 70 75 80 85 90 95 100
Women
Men
year
65 70 75 80 85 90 95 100
year
HRT non user
HRT use <3y
HRT use 3-10y
HRT use >10y
0.12
0.10
0.08
0.06
0.04
0.02
0
0.12
0.10
0.08
0.06
0.04
0.02
0
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A wise man ought to realize that health is his
most valuable possession and learn how to treat
his illnesses by his own judgment.
Hippocrates
A wise menopause physician ought to realize that
health and quality of life are largely to be defined
based on each patient’s judgment.
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Everything possible should be enacted to maintain QoL
after menopause, including, but not limited to, use of
HRT when indicated. Personalization is the key to
success.
Behavioral interventions (such as dietary education,
promotion of a healthy lifestyle, physical activity) or
medical treatments that improve QoL, will likely result
in the long term in reduced incidence of degenerative
disorders.
CONCLUSIONS