nataree

Menopause
• Menopause
–Natural or spontaneous
–Induced
»Chemotherapy Mlc arms tx CA breast

»Radiotherapy
»Surgery oinroi
→

• Risk factors associated with an earlier

menopause
– Smoking
– Positive family history
– Pelvic surgery (including hysterectomy) 2
Estimated risk of gonadal dysfunction with
cytotoxic drugs

Sonmezer M, Oktay K. Hum Reprod Update 2004; 10: 251-66.

Menopause OWNING

– The permanent cessation of menstruation

– Resulting from loss of ovarian follicular
activity follicle
Nwa

– Diagnosed retrospectively following 12

months of amenorrhea
– Association with elevated gonadotrophins
and estrogen deficiency
– The average age of spontaneous
menopause is 51 years
4
 ไดอะแกรมแสดงขอบเขตของสตรีวยั ต่างๆ
-

ldwntuwarlriinndow last up

that Room D

Premenopause
51
,

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.

Climacteric
lwolynium :dw
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,

Hdnodiolqnuwniha .
do so I YwdooriowuwnodoJ 1

Postmenopause

Menopause
transition
อายุ (ปี )

0 10 20 30 40 50 60 70
 Human ovarian reserve

'

ring menopause

0 ruifoitovas

& DJ
MNMW @ a

Daan NM and Fauser BC. Maturitas 2015;82:257-65.

 Ovarian Aging

Daan NM and Fauser BC. Maturitas 2015;82:257-65.

Mean age at natural menopause (95% confidence
interval) stratified by geographical region

Schoenaker DA, et al. Int J Epidemiol 2014;5: 1542-62.

 Life expectancy at birth in the USA
peak bone mass
oiyhau
between 1900 and 2010
30 -35J

Daan NM and Fauser BC. Maturitas 2015;82:257-65.

 rioonnamronriiuoinlrinr :p not final menstrual period

rinwwjos peak bone mass IVHJO to : Nwmrdaio bone

Juan noo
Juiwrvsow

Climacteric 2012;15:105-14. Fertil Steril 2012;97:843-51.

J Clin Endocrinol Metab 2012;97:1159-68. Menopause 2012;19:387-95.
Diagnose menopause and Ioiltlrn
Mdwoiuwlwaomwn

Healthy women aged > 45 years with

menopausal symptoms militiaman cause
odiw
didoofodisoowioioo in : hormone

ilmtahnhwoioslot estradiol into

• Perimenopause
. FSH dx menopause
,

– Vasomotor symptoms and irregular periods

• Menopause
– No period for at least 12 months and are
not using hormonal contraception
– Based on symptoms in women without a
uterus
Lumsden MA. Climacteric 2016;19:426-29.
Diagnose menopause
Healthy women aged > 45 years with
menopausal symptoms

Sex steroids, gonadotropins, inhibin B, or AMH

measurements >> no benefits
– Not further inform the diagnosis
– Not indicate precisely when the final menstrual
period will occur
– Not influence management unless a woman is
seeking fertility
 Prevalence of perimenopause or
postmenopause by age

Median age at perimenopause 47.5 years

Median age at postmenopause 51.3 years
McKinlay SM, et al. Maturitas 1992;14:103-15.
• A 49-yr-old woman was self-referred for possible
estrogen therapy
• She has been experiencing intermittent hot
flashes and difficulty sleeping for the past year,
but the severity and frequency of hot flashes
have increased recently
• She has frequent waking episodes and is finding it
difficult to concentrate
• Menses had occurred approximately every 6–8
wk for the past 2 yr, but her most recent period
was 12 months ago → nwntnwnddiinlaeowmowow
,
48 D

• She has no personal or family history of coronary

heart disease, stroke, venous thromboembolism
• She is a nonsmoker
DX An : charts woinsrnokr * on '1w
'

serious
,
 Signs and symptoms of menopause
• Core symptoms of menopause >) Normand E

www.V braid MVIU

– Vasomotor symptoms
,

50W intends
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→

amrpiOo1mra1nmrnnisvoIestrogenlo1mrndwWwriVestn9eMrnriWniin1Woo1naiuwnestrogennnjs@lNowmaiuVoaiDouiiowuomwinestngenMtrowpvnuddxdowqvnvihyperthyroid.oV

– Genitourinary syndrome
• Other signs and symptoms: bone fracture
• Possible related signs and symptoms (not
proven) jfwdvdwlldiafraovihosmwan Nw Nnownwroulhs

– Mood change, mild depressive symptoms, anxiety,

irritability, arthralgias, loss of libido, palpitations,
skin dryness, fatigue, and reduction in QOL
Stuenkel CA, et al. J Clin Endocrinol Metab 2015;100:3975-4011.
 Vasomotor Symptoms
• Vasomotor symptoms ehdwd
trigger

– Characterized by perspiration, flushing, chills,

clamminess, anxiety, and, on occasion, heart
palpitations
– May interfere with sleep and cause chronic sleep
disruption in some women
ihdonovdwoooiooild wood
dowqvmviiadnmrnt Hwa ANS

• Hot flush draw dilate

– The sudden sensation of extreme heat in the upper

.
.

body, particularly the face, neck, and chest

– Typically last 1–5 minutes
 Vasomotor symptoms
• A sudden sensation of heat centered on the
upper chest and face
• Moderate or severe, the hot flash rapidly
becomes generalized, lasts from 2 to 4 minutes,
and can be associated with profuse perspiration,
palpitations, or anxiety
• Triggers include spicy food or alcohol
www.unlwnwtnu
• At night, vasomotor instability manifests as hot
* son

snfeoviw www.NJV →
oio

flashes or night sweats, which may represent

→ Mind

different physiological mechanisms

Stuenkel CA, et al. J Clin Endocrinol Metab 2015;100:3975-4011.

Ysilviwmo Vojvm

Guttuso T, et al. Maturitas;2012: 213-6.

18
 Cause of hot flashes

Up D to
W
-
nvuuo m
,

Mini orw a: Had

a Mr

Thermoneutral zone (A) and involved neurotransmitter (B)

Krause MS, Nakajima ST. Obstet Gynecol Clin N Am 2015;42:163-79.
 Risk factors for hot flashes (1)
• Women of different ethnic backgrounds
>> genetic polymorphisms >> an effect
on
– The estrogen receptor alpha
– Enzymes involved in the sex-steroid pathways
– Estrogen metabolism
– Circulating estrogen concentration
– Severity of vasomotor symptoms

Krause MS, Nakajima ST. Obstet Gynecol Clin N Am 2015;42:163-79.

 Risk factors for hot flashes (2)
• Obesity
– Adipose tissue acts as a heat insulator
– Make hot flashes worse
• Nicotine
– Antiestrogenic effects
– Women who smoke
• Enter menopause on average 2 to 3 years
earlier than nonsmokers
• A 60% higher risk for hot flashes

Krause MS, Nakajima ST. Obstet Gynecol Clin N Am 2015;42:163-79.

 Risk factors for hot flashes (3)
07 MdW7nnj7

• Negative mood and affect or a history of

child abuse or neglect
–A lack of coping skills when presented
with social and lifestyle stress

Krause MS, Nakajima ST. Obstet Gynecol Clin N Am 2015;42:163-79.

 Risk factors for hot flashes (4)
• Lower socioeconomic position
– May be a true risk factor or be a confounder
– Lower socioeconomic position is associated
with risk factors for more vasomotor
symptoms
• Smoking
• Higher BMI
• Higher stress levels
Krause MS, Nakajima ST. Obstet Gynecol Clin N Am 2015;42:163-79.
 How does menopause affect sleep?

• Multiple awakenings
• Difficulty falling asleep
• Difficulty getting back to sleep
• Menopausal symptoms >> interrupt sleep may
be more troublesome than daytime symptoms
>> should be considered when targeting
therapy

Roberts H and Hickey M. Maturitas 2016;86:53-8.

 Mis RIO 1 rnodw

Differential diagnosis of menopausal symptoms

say
• Hyperthyroidism
uowxwuoneinvnm
,

– Irregular menses, sweating, and mood changes

• Menstrual cycle changes
Eninsovnriwo
– Pregnancy →
oioomwlodooqwnilnn
of JNIJIWWIV

Inaiewa Von fomormionoonoo anti to 6in Nuonwndnri > ) now Not

– Hyperprolactinemia
.

– Thyroid disease
• Sweating symptoms
– Medications, hypoglycemia, carcinoid,
pheochromocytoma, or malignancy Iraq
Martin KA and Manson JE. J Clin Endocrinol Metab 2008;93: 4567-75.
Kaunitz AM and Manson JE. Obstet Gynecol 2015;126:859-76.
 Conditions That May Cause or Mimic
Vasomotor Events

Stuenkel CA, et al. J Clin Endocrinol Metab 2015;100:3975-4011.

What is the natural progression of
vasomotor symptoms during the
transition to menopause?
Relationship between estrogen and a woman’s reproductive
phases and the occurrence of hot flushes
iwvrmtmtsiuw

' n' Elninuo:

µto domrmnuwouiwddoilovwoieowswlnw s I

( ~
Gmo -
2 yr )

tot flush UW

29
 Prevalence of vasomotor symptoms during and after
transition to menopause
Time to or from FMP Pooled prevalence (95%CI)
2 years before FMP 14% (10 to 19)
1 year after FMP WOIMISNMNJHM 56% (50 to 61)
5 years after FMP Wnuwuwn 52
a 29% (22 to 37)
8 years after FMP Returned to baseline

STRAW stage Pooled prevalence (95%CI)

Premenopause 16% (12 to 20)
Early postmenopause (< 4 years after FMP) 60% (57 to 63)
Late postmenopause (5 years after FMP) 44% (34 to 54)

Schleinitz MD, Col NF. J Gen Intern Med 2008;23:1507-13.

Crandall CJ. Evid Based Med 2009 ;14:22.
 The prevalence of menopausal symptoms
among southern Thai women aged 45–65 years
Nwfnoiliatwioo rinlwnmwnlakioornm Haitham
mrmnoqi -2J
orowevmv annum

o
Wvioolw peri

Peeyananjarassri K, et al. Climacteric 2006;9:23-9.

 Genitourinary syndrome of menopause (GSM)

sotwnohwuoininsluk

}
-

'

HWNW complaint
-
Dominion lobby bolwiuwocyzoiu HHIHMA

ooonsi r
too noon his tartan load SI
,
ndaindu

bteoaoonshv Nndw IN ni Wodosaddn HHJ

,

normal flora an outdoor linmromdvda No

Stuenkel CA, et al. J Clin Endocrinol Metab 2015;100:3975-4011.

Genitourinary syndrome of menopause

Gandh J, et al. Am J Obstet Gynecol 2016;215:704-11.

Interference of VVA symptoms

I
mw Unto ihtv

to ) noon 1165 → nmn

SI 11W
\ '

so stay sn - link

Percent of women reporting

interference
Kingsberg SA, et al. J Sex Med 2013;10:1790-9.
 The prevalence of menopausal symptoms
among southern Thai women aged 45–65 years
a mrmoorvvoivoidvwwfds estrogen ninny oimrnr iwmmwiooo ,
.

Vloolvi @ to iwn :
#
,
won VEO

TJ Nsohl
,

Peeyananjarassri K, et al. Climacteric 2006;9:23-9.

Prevalence of genitourinary menopausal
syndrome (GSM)

ejguioig , do no :

Palma F, et al. Maturitas 2016;83:40-4.

 quality of life

Effect of menopausal symptoms on QoL

TAM Vg nilvisfnmwodnueinjz

Peeyananjarassri K, et al. Climacteric 2006;9:23-9.

 Treatment of vasomotor symptoms

• Life style changes

• Nonprescription medications or over the
counter drug
• Nonhormonal prescription medications
• Hormonal therapy

Shifren JL and Schiff I. Obstet Gynecol 2010;115:839-55.

Hwihh llriniswniisoi
Lifestyle changes (1)
on nilloidawilovnrii

Cooling body core temperature: keep the thermostat

low
• To wear light, layered clothing
• Use portable fans at the desk and bedside
• Maintaining a lower ambient temperature
• Consuming cool drinks
Avoiding hot and spicy foods
Avoiding consumption of alcohol and caffeine

Sturdee DW, et al. Climacteric 2011;14:302-20. NAMS. Menopause 2012;19:257-71.

Shifren JL and Schiff I. Obstet Gynecol 2010;115:839-55.
Fisher TE and Chervenak JL. Maturitas;2012: 217-20.
39
 Lifestyle changes (2)
• Maintaining a healthy weight
autumn
• Exerciseonsivzunvsiri
l
aonriownvw
> .

• Relaxing therapies: yoga, massage, meditation, slow

breathing or leisurely baths
• Mind-body therapies
– Relaxation, meditation, participation in group
education
– Decrease norepinephrine levels and widening the
thermoregulatory zone
• Ninonrrwnd 'VoUN°7

Sturdee DW, et al. Climacteric 2011;14:302-20. NAMS. Menopause 2012;19:257-71.

Shifren JL and Schiff I. Obstet Gynecol 2010;115:839-55.
Fisher TE and Chervenak JL. Maturitas;2012: 217-20.
40
 Nonprescription medication
• Phytoestrogens: isoflavones
• Black cohosh
• Vitamin E
tsimhsnn placebo

• Efficacy greater than placebo unproven

Eden JA. Maturitas 2012;72:157-9. Nelson HD, et al. JAMA 2006;295:2057-71.
Shifren JL and Schiff I. Obstet Gynecol 2010;115:839-55.
Leach MJ, Moore V. Cochrane Database Syst Rev 2012, Issue 9.
Lethaby A, et al. Cochrane Database Syst Rev 2013, Issue 1.
 Nonhormonal prescription medications
• SSRIs and SNRIs: paroxetine, venlafaxine,
desvenlafaxine
• Clonidine
• Gabapentin
• Provide evidence for efficacy but effects are less
than for estrogen
• Adverse effects and cost may restrict use
• Not approved by U.S. Food and Drug Administration
for treatment of vasomotor symptoms
Nelson HD, et al. JAMA 2006;295:2057-71. Guttuso T Jr. Maturitas 2012 ;72:6-12.
Shifren JL and Schiff I. Obstet Gynecol 2010;115:839-55.
What nonhormonal treatments are effective
for the treatment of vasomotor symptoms?
tulnolw ouli
'

n'

ACOG Practice Bulletin. Obstet Gynecol 2014; 123:202-16.

 Hormonal therapy
• Highly effective in alleviating hot flushes
.

and night sweats

HT and hot flushes: frequency per week Bm

Cochrane Database of Systematic Reviews 2009, Issue 1.

HT and hot flushes: severity

Cochrane Database of Systematic Reviews 2009, Issue 1.

ACOG Practice Bulletin. Obstet Gynecol 2014; 123:202-16.
 enriuiww thermoneutral zone lrinoigtiw

Asymptomatic women Symptomatic women

Normal temperature Thermoregulatory

regulation dysfunction

Narrowed thermoneutral zone

48
• A 49-yr-old woman with hot flushes
–Life style changes
–Nonprescription medications or over
the counter drug
–Nonhormonal prescription
medications
–Hormonal therapy
Recommendations on postmenopausal HT
dim Vrioiiwrvnownwrovvno Nbmnnmvoinv otimuno ; so

oimrrwnsounow
IN Drouin vowoevmmrrnoldvoloi
,

g
Treatment of vasomotor symptoms
f.
run .

sitx

Treatment of vaginal symptoms

Prevention of osteoporosis

J Clin Endocrinol Metab 2010;95 (Suppl 1) s1-s66.

Maturitas 2008;61:227- 32.
de Villiers TJ, et al. Climacteric 2013;16:316-37.
NAMS. Menopause 2012;19:257-71.
Recommendations for HT use

Baber RJ. Climacteric 2016;19:109-150.

Roberts H and Hickey M. Maturitas 2016;86:53-8.
 611AM WNMMUNV 010W ( To
,

a Contraindications to HT use
Adm IWW www.trnsihiuwomnuwnliinoioo no pregnancy ooniow

–Pregnancy
-
* check at
th n' owisweo )
mammogram
e Nwoionrigiw
–Estrogen dependent cancer: breast or *

endometrial cancer
n
siirvrinrodonoonanvnn e bx

risk assessment :
Framingham sure

–Cardiovascular disease: CHD or stroke

–Thromboembolic disorders lgnaminvrioiv
–Active liver or gall bladder disease

Shifren JL and Schiff I. Obstet Gynecol 2010;115: 839-55.

Oral estrogen and progestogen
products available in the US
Nonoral estrogen and progestogen
products available in the US
For how long should women take HT?
Winnil

• As long as the benefits outweigh the risks

woolmruwy lionn woinnn undo
→
oonniosmvwo :p )nv www.nuhwuhnw
www.anmroionwiuynwn/lwniNw
“Individualized based on the severity of ioinnw
symptoms and current benefit-risk ratio
consideration”
estrogen

s IE nd oovlsiloi To oinimiww WT iddoaoonandnn → Isidor .li

pt
: , :
, .

(
laioaoonnvtvn
Nov
:

anwouruuaniiov mini .
a8

Roberts H and Hickey M. Maturitas 2016;86:53-8.

How should the genitourinary syndrome
of menopause be managed?
 Treatments for genitourinary syndrome
for
nrtmygr of menopause
hormone

hormone
www.nlrirooaaoannirioodseioo
:p
dirougvowioyuosnoonnnldiooiuvnorna
-

UNJSIIIWM 'ow
www.rfonwvtusoitw → Moisan bhuoioniw 9
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first
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ftear WHMMIIUJ KWJ
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mMowNIidmrooohM1u7NlkVniowDsyqNmrnaodinkygdmowdon9dmenduN.oHPohtVWHoimr1uhnwynrwhormone-regeH@MMnwo1dwenb1wIoiVovtioooiwhis1w8ounnndwoynouswascNwIWsoiHNdusnVnoo.Ir EO
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Gynoform ( lactobacilli )
potency M 1) l way Nw superficial all
Es
pambasallbqsal cell
C

Palacios S, et al. climacteric 2015;18 suppl1:23-9.

Classification of Government-Approved
Vaginal Estrogens

Stuenkel CA, et al. J Clin Endocrinol Metab 2015;100:3975-4011.

Risk of hormone therapy
 Risks and benefits of HT
Decision making

Benefits Risks
- Treatment of - CHD
lieu
menopausal symptoms - VTE
- Prevention of bone - Stroke
loss - Breast cancer
Hormone therapy and breast cancer risk
9 risk a breast iwn : estrogen Dwanb all lmiww
 E DNOMNOW pVmU undiihtojiynuo I to breast ,
endometrim

Paw into
na risk Winn CA endometrial hoist oinwngnilw'd hide Hdoioioivsn

Breast cancer: combined HT versus placebo

oios add

dnlii tx lvwiw no 58 Mioswoivwui

osteoporosis : →

tx vasomotor :
Nunn 'ow 5 T

→ and Nntwlwwnmwidvo

→
iwzinvoowlwwnnwldw
 indication

i. iwrnmnwrowgvowyulwsmn
lidowdloiwa

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hliiowdooihla pivot www.wsbwwbihwuw

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risk A breast

minion n' rwhin

mammogram
and
ruin him oirosnahwhwwdahldwo mammogram

Wiw e nihirinmoumtwn author And'nVw of

 Recommendation
• Short term use of HT can relieve
menopausal symptoms and does not
appear to affect the breast cancer risk
VTE: combined HT versus placebo
n' www.waamdunjn.inhhinniumbiiIND
nnwidnnomnh
renews thrombosis

Marjoribanks J, et al. Cochrane Database of Systematic Reviews 2017, Issue 1.

CHD: combined HT versus placebo
frisk frnasoabiodnn
nfuilillriddov

moo screening CHD

score
Framingham

NCEP 3

Didnnwidssritw now

Marjoribanks J, et al. Cochrane Database of Systematic Reviews 2017, Issue 1.

 Stroke: combined HT versus placebo

J IWIWN into

|
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-
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3 Judo stroke

An s J CA breast

thrombosis
'

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vomidainwni IN nor N
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-

60 0 spme
-

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Marjoribanks J, et al. Cochrane Database of Systematic Reviews 2017, Issue 1.

 Hypotheses of increased CHD risk

Timing hypothesis Window hypothesis

Route Dose

Types of progestogens Types of estrogens

 The timing hypothesis
• Window hypothesis

• Younger women would benefit

• Hormone therapy given later will have

adverse effect
 Effects of hormone therapy on CVD by age and
time initiation

Age (years) Years since menopause

50-59 60-69 70-79 <10 10-19 > 20
0.93 0.98 1.26 0.76 1.10 1.28
CHD (0.65-1.33) (0.79-1.21) (1.00-1.59) (0.50-1.16) (0.84-1.45) (1.03-1.58)
1.13 1.50 1.21 1.77 1.23 1.26
Stroke (0.73-1.76) (1.17-1.92) (0.93-1.58) (1.05-2.98) (0.92-1.66) (0.98-1.62)

Subgroup hrdwolywovoldihwanwldn

Initiation hormone therapy in younger women does not

increase CHD and stroke risk

Rossouw JE, et al. JAMA 2007;297:1465-77.

 Recommendations (1)
• HT must be individualized and tailored
laawlvwwnmohlnwronir
Vouiw
according to lriwvnfwriufnvntinrw

– Symptoms and the need for prevention

– Personal and family history
– Results of relevant investigations
– The woman’s preferences and expectations
• The risks and benefits of HT differ for women
during the menopause transition compared to
those for older women
Inlaid on www.vaulwdiboiruoasoanuilwdmnunwrwtniosm/uwhuoyoi1woNwWrrooahnNvMr:WnfMnrimenopavse1ddaW
(

Recommendations (2)
Mv > 45 armored
, Astros treat
ipinwfrriosm HIHNO

• Dosage should be titrated to the lowest effective

dose treat
/
• Progestogen should be added to systemic estrogen
for all women with a uterus to prevent endometrial
www.vnvdosontdnrimlutwdnw

hyperplasia and cancer

• Low-dose topical vaginal estrogens
– Relief of urogenital atrophy
– Systemically absorbed but not at levels that
stimulate the endometrium
– Concurrent progestogen is not required
73
 Recommendations (3)
• Women taking HT should have at least an
annual consultation to include
– A physical examination
– Update of medical and family history
– Relevant laboratory and imaging investigations
– A discussion on lifestyle and strategies to prevent
or reduce chronic disease

74
Health concerns of menopausal women

Shifren JL and Schiff I. Obstet Gynecol 2010;115:839-55.

Krause MS, Nakajima ST. Obstet Gynecol Clin N Am 2015;42:163-79.
Krause MS, Nakajima ST. Obstet Gynecol Clin N Am 2015;42:163-79.
 The Physician’s role and approach
ermine bacilli

bacilli
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Nb A M W Not
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Questions?

79