Download Menopausal Transition

Menopausal Transition
彰化基督教醫院
主治醫師黃志成
Definitions
zMenopause
{A point in time that follows 1 year after the
cessation of menstruation
zPostmenopause
• Those years following this point
zPremature ovarian failure
{Cessation of menses before age 40
{Associated with an elevated follicle-stimulating
hormone (FSH) level
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Definitions
zPerimenopause or climacteric
{The time period in the late reproductive years
{Usually late 40s to early 50s
zBegins with menstrual cycle irregularity
zExtends to 1 year after permanent cessation of
menses
{The more correct terminology for this time is
menopausal transition
zTypically develops over a span of 4 to 7 years
zAverage age at its onset is 47 years
Symptoms associated with menopausal
transition
zChanges in menstrual patterns
{Shorter cycles are typical (by 2-7 days)
{Longer cycles are possible
zVasomotor symptoms
{Hot flushes
{Night sweats
{Sleep disturbances
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Symptoms associated with menopausal
transition
zPsychological and mental disturbances
{Worsening premenstrual syndrome
{Depression
{Irritability
{Mood swings
{Loss of concentration
{Poor memory
zSexual dysfunction
{Vaginal dryness
{Decreased libido
Symptoms associated with menopausal
transition
zSomatic symptoms
{Headache
{Dizziness
{Palpitations
{Breast pain and enlargement
{Joint aches and back pain
zOther symptoms
{Urinary symptoms
{Dry, itchy skin
{Weight gain
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Evaluation of abnormal bleeding
zSonography
{In postmenopausal women with abnormal
bleeding
zEndometrial biopsy is not required
• If the endometrial thickness is less than 5 mm
Evaluation of abnormal bleeding
zEndometrial biopsy is indicated in
{A premenopausal patient
zIf a clinical history suggests long-term unopposed
estrogen exposure, even if the endometrial thickness
is "normal" (5 to 12 mm)
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Evaluation of abnormal bleeding
zHysteroscopy
{Evaluation of focal intrauterine lesions
{Targeted biopsy of specific lesions such as
zSubmucous leiomyomas
zEndometrial polyps
zFocal areas of endometrial hyperplasia
zEndometrial cancer
Vasomotor symptoms
zHot flashes, hot flushes, and night sweats
zThe incidence of hot flushes
{10 percent during the premenopausal period
{Approximately 50 percent after cessation of
menses
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Vasomotor symptoms
zHot flushes
{Begin an average of 2 years before the FMP
{85 percent of women who experience them will
continue to experience them for more than 1
year
{Of these women
z25 to 50 percent will have hot flushes for 5 years
z15 percent may experience them for >15 years
Vasomotor symptoms
z Hot flush
{Generally lasts 1 to 5 minutes
{Skin temperatures rise because of peripheral
vasodilation
z This change is particularly marked in the fingers and toes
• Where skin temperature can increase 10 to 15°C
{Most women sense a sudden wave of heat
z Spreads over the body
• Particularly on the upper body and face
z Sweating begins primarily on the upper body
z Sweating has been observed in women during
90 percent of hot flushes
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Vasomotor symptoms
zIncreases in both awake and sleep systolic
blood pressure are noted with hot flushes
zHeart rate increases 7 to 15 beats per
minute
{At approximately the same time as peripheral
vasodilatation and sweating
zHeart rate and skin blood flow
{Usually peak within 3 minutes of the onset of
the hot flush
Vasomotor symptoms
zSimultaneously with sweating and
peripheral vasodilation
{The metabolic rate also significantly rises
zHot flushes may also be accompanied by
{Palpitations, anxiety, irritability, and panic
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Vasomotor symptoms
zFive to 9 minutes after a hot flush begins,
{Core temperature decreases 0.1 to 0.9°C
zDue to heat loss from perspiration and increased
peripheral vasodilation
zIf the heat loss and sweating is significant
{May experience chills
zSkin temperature gradually returns to
normal
{Sometimes taking 30 minutes or longer
Pathophysiology of vasomoter symptoms
zThe medial preoptic area of the
hypothalamus
{Contains the thermoregulatory nucleus
{Responsible for regulating perspiration and
vasodilatation
zIf exposed to temperature changes
{This nucleus activates these heat dissipation
mechanisms
zThese maintain core body temperature in a regulated
normal range
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Pathophysiology of vasomoter symptoms
zEstrogens play a vital role in the
development of hot flushes
zWomen with gonadal dysgenesis (Turner
syndrome)
{Who lack normal estrogen levels
{Do not experience hot flushes
zUnless first exposed to estrogen
• Then withdrawn from treatment
Pathophysiology of vasomoter symptoms
zNeurotransmitter
{Altered neurotransmitter concentrations
zMay create
• A narrow thermoregulatory zone and a lowered sweating
threshold
y Even subtle changes in core body temperature may
trigger heat loss mechanisms
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Pathophysiology of vasomoter symptoms
zNorepinephrine
{The primary neurotransmitter
zResponsible for
• Lowering the thermoregulatory setpoint
zTriggering the
• Heat loss mechanisms associated with hot flushes
{Plasma levels of norepinephrine metabolites
zIncreased before and during hot flushes
Pathophysiology of vasomoter symptoms
zThat norepinephrine injections
{Can increase core body temperature
zInduce a heat loss response
zConversely
{Medications that decrease norepinephrine
levels
zMay reduce vasomotor symptoms
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Pathophysiology of vasomoter symptoms
z Estrogens
{Are known to modulate adrenergic receptors in many
tissues
z Freedman and colleagues (2001) suggested
{Hypothalamic 2-adrenergic receptors are decreased
z By menopause-related decreases in estrogen levels
{A decline in presynaptic 2-adrenergic receptors
z Leads to increased norepinephrine levels
• Thereby causing vasomotor symptoms.
Pathophysiology of vasomoter symptoms
zSerotonin
{Estrogen withdrawal is associated with a
decreased blood serotonin level
zUpregulation of serotonin receptors in the
hypothalamus
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Pathophysiology of vasomoter symptoms
zThat reductions and significant fluctuations
in estradiol levels
{A decline in inhibitory presynaptic 2-adrenergic
receptors
{An increase in hypothalamic norepinephrine
and serotonin release
zNorepinephrine and serotonin lower the setpoint in
the thermoregulatory nucleus
• Allows heat loss mechanisms to be triggered by subtle
changes in core body temperature
Sleep Dysfunction and Fatigue
zWomen may awake several times during
the night
{May be drenched in sweat
zDisturbed sleep can lead to
{Fatigue, irritability, depressive symptoms,
cognitive dysfunction, and impairment in daily
functioning
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Fatigue prevention instructions
z Obtain adequate sleep every night
z Exercise regularly to reduce stress
z Avoid long work hours and maintain your
personal schedule
z If stress is environmental, take vacations, switch
jobs, or approach your company or family to
help resolve sources of your stress
z Limit intake of alcohol, drugs, and nicotine
z Eat a healthy and well-balanced diet
z Drink adequate amounts water (8 to 10 glasses)
during the early part of the day
z Consider seeing a specialist in menopausal
medicine
Hormone treatment
彰化基督教醫院
主治醫師黃志成
13
The mature woman
zThe typical "mature woman" is
{Aged 40 years or older and has completed
childbearing
{During their late 40s
zMost women enter menopausal transition
zThis period of physiologic change is usually
completed between ages 51 and 56
Current Approach to Hormone
Replacement Administration
zSummary of Risks and Benefits
{Suggest that
zOnce coronary heart disease is established
• Hormone therapy (HT) has no effect in reversing disease
progression
{The incidence of cardiovascular events
zCan potentially increase in older groups due to an
increased risk for blood clots
{Benefits are noted with HT
zIncreased bone mineral density and decreased rates
of fracture and colorectal cancer
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Summary of Current Use Indications
zHT is indicated today only for treatment of
{Vasomotor symptoms
{Vaginal atrophy
{Osteoporosis prevention or treatment
zShould be prescribed
{In the lowest effective dose
{For the shortest period of time
Estrogen should not be used in the
following conditions
z
z
z
z
z
z
z
z
Undiagnosed abnormal genital bleeding
Known, suspected, or history of breast cancer
Known or suspected estrogen-dependent neoplasia
Active deep vein thrombosis, pulmonary embolism, or
history of these conditions
Active or recent (e.g., within the past year) arterial
thromboembolic disease (e.g., stroke or myocardial
infarction)
Liver dysfunction or disease
Known hypersensitivity to the ingredients of the estrogen
preparation
Known or suspected pregnancy
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Estrogen should be used with caution in
women with the following conditons
z Dementia
z Gallbladder disease
z Hypertriglyceridemia
z Prior cholestatic jaundice
z Hypothyroidism
z Fluid retention plus cardiac or renal dysfunction
z Severe hypocalcemia
z Prior endometriosis
z Hepatic hemangiomas
"Bioidentical" Hormones
zThe FDA pronounced:
{"Other doses of CEE and MPA, and other
combinations and dosage forms of estrogens
and progestins were not studied in the WHI
clinical trials, and in the absence of comparable
data, these risks should be assumed to be
similar".
zThus, these hormones cannot be assumed
to be safer than conventional
pharmaceutical estrogen or progestins
16
Nonhormonal agents used as therapy for
vasomotor symptoms
z Prescriptions (brand
name)
z SSRI
{ Venlafaxine (effexor)
{ Fluoxetine (prozac,
sarafem)
{ Paroxetine (paxil)
z
z
z
z
Clonidine (catapres)
Gabapentin (neurontin)
Mirtazapine (remeron)
Trazodone (desyrel)
z
z
z
z
Nonprescription
Black cohosh
Dong quai
Red clover
{ Isoflavones
z Soy isoflavones
z Vitamin E
SSRI = selective serotonin reuptake inhibitor
Complementary and Alternative Medicine
zPhytoestrogens (isoflavones)
{Plant-derived compounds
{Bind to estrogen receptors
zHave both estrogen agonist and antagonist
properties
{They are found in soy products and red clover
(苜蓿)
{Small studies evaluating their effectiveness for
the treatment of vasomotor symptoms
zNo efficacy or mixed results
17
Complementary and Alternative Medicine
zSoy products
{The effects of soy protein found in various food
preparations are not bioequivalent
{For example
zThe alcohol processing
• Often used in the manufacture of tofu and soymilk
• Removes the biologically active forms
y The aglyconic isoflavones
Complementary and Alternative Medicine
zFlaxseed(亞麻籽) or flaxseed oil (Linum
usitatissimum)
{Rich in -linolenic acid, a form of omega-3 fatty
acid
{Also known as linseed, flaxseed is touted(招徠)
to reduce
zInflammation, bone turnover, heart disease, cancer,
diabetes, and cholesterol levels
zFor perimenopausal women, it also is purported(傳說
的) to protect against breast cancer, hot flushes, and
mood disturbances
18
Complementary and Alternative Medicine
zRed Clover
{It contains at least four estrogenic isoflavones
zMarketed as a source of phytoestrogens
{A randomized controlled trial of 252 women
studied hot flush frequency in women given red
clover isoflavone extracts and placebo over 12
weeks
zNo significant change in hot flush frequency was
reported between groups receiving isoflavones and
those given placebo
Complementary and Alternative Medicine
zDong Quai
{Within traditional Chinese medicine (TCM)
practice
zDong quai is suggested to
• Regulate and balance the menstrual cycle, strengthen
the uterus, and enrich the blood
zIt is also said to exert estrogenic activity
{However, its benefit cannot be substantiated
based on available evidence.
19
Complementary and Alternative Medicine
zBlack Cohosh(升麻)
{The root of the herb Cimifuga racemosa is also
thought to have estrogenic properties
zThe mechanism of action is unknown
{In a randomized placebo-controlled trial in 85
women
zIt did not decrease the frequency of vasomotor
symptoms compared with placebo
Complementary and Alternative Medicine
zPhytoprogestins
{Extracts, tablets, and creams derived from
yams(山芋類植物;山藥;馬鈴薯)
zTo be progesterone substitutes
zA natural source of dehydroepiandrosterone (DHEA)
{Based on the lack of bioavailability
zThe hormones in wild and Mexican yam would not be
expected to have efficacy
{No published reports demonstrating the
effectiveness of wild yam cream for
postmenopausal symptoms
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Complementary and Alternative Medicine
zVitamin E
{In 125 women with a history of breast cancer
zVitamin E produced a 25-percent reduction in hot
flushes compared with a 22-percent reduction with
placebo
zA decrease of one hot flush per person per day
The end
IMS updated recommendations
on postmenopausal hormone
therapy
IMS: international menopause society
Climateric 2007;10:181-194
彰化基督教醫院
主治醫師黃志成
21
Introduction
zThese recommendations were reviewed
and discussed by representatives of more
than 60 National and Regional Menopause
Socoieties from all continents
Governing principles
zA spontaneous or iatrogenic menopause
{Before the age of 45 years and particularly
before 40
zAre at higher risk for cardiovascular disease and
osteoporosis
zHormone replacement should be given at least until
the normal age of menopause
22
Governing principles
zDosage should be titrated to the lowest
effective dose
zLower doses of HT
{Can maintain quality of life in a large proportion
of users
{Long-term data regarding fracture risk and
cardiovascular implications
zStill lacking
Governing principles
zLow-dose vaginal estrogens
{Do not require progestogen co-medication
zAndrogen replacement
{Reserved for women with clinical signs and
symptoms of androgen insufficiency
{Bilateral oophorectmy or adrenal failure
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Benefits of hormone therapy
zEffective in preventing the bone loss
zEven lower than standard-dose
preprarations
{Maintain a positive influence on bone indices
zStandard-dose HT
{Not recommended for the sole purpose of the
prevention of fractures after the age of 60 years
Postmenopausal osteoporosis
Benefits of hormone therapy
zThe initiation of HT dose not cause early
harm and in fact reduces cardiovascular
morbidity and mortality in
{Women less than 60 year old
{Recently menopausal
{Without prevalent cardiovasular disease
Cardiovascular disease
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Benefits of hormone therapy
zContinuation of HT beyond the age of 60
{Should be decided as a part of the overall riskbenefit analysis
Cardiovascular disease
Benefits of hormone therapy
zBenefits for connective tissue, skin, joints
and intervertebral disks
zReduce the risk of colon cancer
zInitiated around the time of menopause or
by younger postmenopausal women
{Reduced risk of Alzheimer’s disease
Other benefits
25
Potential serious adverse effects of
hormone therapy
zMillion Women Study
{Risk was increased as early as the first year
zWomen’s Health Initiative(WHI) study
{No increased risk
zIn women initiating HT, for up to 7 years
Breast cancer
Potential serious adverse effects of
hormone therapy
zWHI and Nurses’ Health Study suggest
{Long-term estrogen-only for 7 and 15 years,
respectively
zDoes not increase the risk of breast cancer in
American women
zRecent European observational studies
{Risk may increase after 5 years
Breast cancer
26
Potential serious adverse effects of
hormone therapy
zUnopposed estrogen administration
{Dose-related stimulation of the endometrium
zContinuous combined estrogenprogestogen regimens
{A lower incidence of endometrial hyperplasia
and cancer than normal population
Endometrial cancer
Potential serious adverse effects of
hormone therapy
zIncreases with age, obesity and
thrombophilia
zStandard-dose HT
{Transient slightly increased risk of coronary
events
zRiks of stroke
{Correlated with age
zIncrease the risk after age of 60
Thromboembolism, Cardiovascular events
27
Conclusion
zThe safety of HT
{Depends on age
zYounger than 60 years old
• Should not be concerned about the safety profile of HT
The end
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