Professional Documents
Culture Documents
Menopause
Georges El-Kehdy, MD
26/03/2015
Hormonal Production
Absence of follicles
Decreased ovarian volume
Gonadotropins are increased
Androgens are decreased
Estrogens are decreased
Androgens/estrogens ratio is increased
with increased incidence of hirsutism
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GONADOTROPINS
ANDROGENS
Androstenedione
Production is decreased by 50%
Origin is mainly adrenal with minimal ovarian
DHEA and DHEAS
Production is decreased by 70%
Origin is adrenal
Testosterone
Production is decreased by 25%
Origin is ovarian
Ovarian production is increased compared with
premenopausal production
FSH stimulates ovarian stromal tissue
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ESTROGENS
Estrogen production is decreased
Estrone level is higher than estradiol level
E1=30-70pg/ml
E2=10-20pg/ml
Origin is from peripheral conversion by
aromatization of androstenedione to
estrone and than to estradiol
Vasomotor symptoms
Atrophic changes
Psychophysiologic effects
Cognition and Alzheimer's disease
Cardiovascular disease
Osteoporosis
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Intermediate/late
Hot flushes
Dyspareunia
Night sweats
Loss of libido
Insomnia
Urethral syndrome
Anxiety/irritability
Vaginal atrophy
Memory loss
Cardiovascular disease
Poor concentration
Osteoporosis
Mood changes
Climacteric complaints
By menopausal status
Pre
Vasomotor symptoms
Peri
Depressive mood
Post
Anxiety/fears
Sleep problems
Sexual problems
Cognitive difficulties
0
20
40
60
80
100
Hunter, 1988
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Vasomotor Symptoms
(VMS)
Thebeginningisasubjectivefeelingofintenseheat.
Theperceptionbeginsinthethermoregulatory
centerlocatedinthehypothalamus.
Nextisareddeningoftheskin,firstofthehead,and
neck,andthentheanteriorchest:vasodilatory
responsetodissipatetheheat.
Nextisincreaseinperspiration,evaporation,and
coolingphase.
Vasomotor Symptoms
(VMS)
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Temperature in VMS
Vasomotor Symptoms
(VMS)
Averageduration:23min
Averagefrequency:1every23hours
Intensity:variable
Severe:interfereswithactivity,oftenassociated
with profusesweating
Moderate:perceptiblebutdoesnotinterrupt
activity
Mild:transientrednessoftheskin
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Thermoregulation
EndocrinologyofVMS
DecreaseinEstrogens:+
LHpulses:?
OpioidergicSystem:?
NorEpinephrin:+,butinthebrain[measured
throughitsmetabolite3methoxy4
hydroxyphenylglycol(MHPG)]Adrenergic
Brainreceptor(modulatedbyEstrogen)
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Vasomotor Symptoms
(VMS)
The prevalence of hot flashes varies with culture and
ethnicity.
Some cultures do not have a word to describe VMS
Up to 75% of American women report them and 26% to
60% rate them as severe.
They peak around the final menstruation
One third of women in late reproductive age, and 20% to
30% of those in their 60s and 70s experience VMS
Number of Subjects
45
40
35
30
25
20
15
10
5
0
10
12
14
16
18
20
22
24
28
30
36
41
Years
Mean age of natural menopause was 49.5 years; mean age of surgical menopause was 43.7 years.
Kronenberg F. Ann NY Acad Sci. 1990;592:52-86. Used with permission.
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MENOPAUSE
Impact of estrogen deprivation
EFFECTS ON COGNITIVE FUNCTION
Decreased memory,decreased cognitive
function and increased incidence of
Alzheimer disease are mainly in relation
with aging
Estrogen deprivation might have a role
because ERT might improve these effects
by protection of CNS cells
10
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MENOPAUSE
Impact of estrogen deprivation
PSYCO-PHYSIOLOGIC EFFECTS
Depression is not increased with
menopause
Emotional stability is disrupted by poor
sleep pattern which gets worse with aging
and menopause
HRT is indicated for severe hot flushes
MENOPAUSE
Impact of estrogen deprivation
CARDIOVASCULAR DISEASE
Risk of coronary heart disease
CHD is one of the leading causes of death in
women following cancer
Risk of CHD is over 3.5 times in men that of
women
With increasing age this advantage is gradually
lost (role of estrogen deprivation)
Lipid profile changes
HDL cholesterol is higher in women then in men
and does not change with menopause
LDL cholesterol is lower in females than in males
but increases after the menopause
11
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MENOPAUSE
Impact of estrogen deprivation
OSTEOPOROSIS
MENOPAUSE
Hormonal Replacement
Therapy (HRT)
TRADITIONAL INDICATIONS OF HORMONAL
REPLACEMENT THERAPY
Menopausal symptoms
Prevention of:
Primary and secondary coronary heart
disease (CHD)
Osteoporosis
Alzheimer disease
12
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MENOPAUSE
Hormonal Replacement
Therapy (HRT)
QUESTIONS ABOUT HRT
How effective in CHD and osteoporosis
What is the risk of breast cancer
What is the risk of thrombo-embolic
disease
MENOPAUSE
Hormonal Replacement
Therapy (HRT)
PREVIOUS STUDIES
13
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MENOPAUSE
Hormonal Replacement
Therapy (HRT)
RECENT STUDIES
Meta-analysis
RCT: Randomized
Controlled
Trials
MENOPAUSE
Hormonal Replacement
Therapy (HRT)
UPDATES ON HRT
14
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MENOPAUSE
Hormonal Replacement
Therapy (HRT)
MENOPAUSE
HRT
Protection against CHD
Impact of lipid profile
LDL-cholesterol
decreased
HDL-cholesterol
increased
Triglycerides
increased
15
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16
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17
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18
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Not increased
Increased (RR=1.46)
Not decreased
19
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20
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relative risk
2.5
2
HERS
HERS II
1.5
1
0.5
0
4.00
5.00
6.00
years
21
26/03/2015
CONCLUSIONS
Risks of HRT
2.5
relative risk
2
1.5
TE
CHD
Breast K
1
0.5
0
CONCLUSIONS
Benefits of HRT
22
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CONCLUSIONS
Decisions for HRT
Dont start HRT if menopausal symptoms are
absent
Start HRT if menopausal symptoms are
affection the quality of life
Resume HRT if menopausal symptoms
reappear
Discontinue HRT if no menopausal
symptoms and use alternatives for
osteoporosis prevention or treatment
Definition of QOL
Global sense of self-satisfaction
Sense of well-being
Patients perception of her interest in life
Maintaining satisfactory interpersonal
relationships
Perception of physical and psychological
wellness
Satisfaction with position in life in the context
of culture and value systems
Utian WH, et al. Menopause. 2002;9:402-10.
WHO Division of Mental Health. 1993.
23
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Phytoestrogens
Megestrol
SSRI/SNRI therapy
Gabapentin
CoreBodyTemperature
Exercise
BodyMassIndex
Smoking
RelaxationTechniques
24
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Post-Menopausal Treatment
Efficacy
Safety
Endometrial cancer
Breast cancer
Non-Hormonal Treatment
Pharmacological
Antidepressants
Anticonvulsants
Antihypertensive
Vitamin E
Herbal-Nutritional
Black Cohosh
Phytoestrogens
Soy
Red Clover
Dong quai
Ginseng
Evening Primrose
Kava
25