MENOPAUSE

Sri Ratna D

Department Obstetri and Ginecology FK UNAIR-RSU DR

SOETOMO
SURABAYA

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TUJUAN PEMBELAJARAN
Mengetahui batasan menopause
Mengetahui keluhan pada menopause
Mengetahui tata laksana menopause

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Human Female Life Stages

PUBERTY (Growth Spurt-Thelarche-

Pubarche-
Menarche)
PERIMENOPAUSE

□ MENOPAUSE

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The decreasing follicle pool and age-related decline in

female
fertility.

Follicle
Number

1,000,000

100,000
Birth
10,000

1,000
18
Optimal Fertility

Age (yrs)
Decreased Fertility

End of Fertility

Irregular Cycles

31
37
41
45 51

Menopause

E.R. TE VELDE ET AL., 1998

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Oocyte reserve

Pregnancy 20th weeks : 6-7 millions

Born

□ Puberty
□ Menopouse
: 1 - 2 millions

: 300 thousands
: empty

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FOLLICLE SELECTION
 FSH/LH growth factors

growth
??

selection

no selection

pre-antral early antral small antral

FSH
FSH/LH
growth
LH

ovulation

factors

PCOS
anovulatory
atresia

pre-ovulatory
corpus luteum

LH
recruitment
growth
selection
dominant follicle development
ovulation

FIGURE 15.1. Schematic representations of gonadotropin-

independent and -depen- dent stages of ovarian follicular
development and the complex interactions between
gonadotropins, growth factors, and the processes of follicular
recruitment, selection, growth and differentiation, and
ovulation, as well as corpus luteum function. (See text.)
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TERMINOLOGI

□ Menopause from Greek words

"Pausis" (cessation) and "men" from
mensis (month)
of
Menopause is the permanent
cessation reproductive fertility
occurring some time before the end of
the natural lifespan.
The term was originally coined to describe
this reproductive change in human
females, where the end of fertility is
traditionally indicated by the permanent
stopping of monthly menstruation or
"menses".

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In adult human females who still have a

uterus, and who are not pregnant or
lactating, postmenopause is identified
by a permanent (at least one year's)
absence of monthly periods or
menstruation.
☐ In
or

In women without a uterus,

menopause postmenopause is
identified by a very high FSH
level.

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Perimenopause: meaning "around

menopause"

Perimenopause is the term

describing the menopause transition
years.
In women who have a uterus,
perimenopause describes the years
both before and after the final
period.
During perimenopause, the
production of most of the
reproductive hormones, including
the estrogens, progesterone and
testosterone, diminishes and
becomes more irregular, often with
wide and unpredictable fluctuations in
levels.

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Perimenopause.....
During this period, fertility diminishes, but is
not considered to reach zero until the official date of
menopause.

The official date is determined retroactively, 12

months after the last appearance of
menstrual blood. Signs and effects of the
menopause transition can begin as early as
age 35, although most women become aware of
the transition in their mid to late 40s, often many
years after the actual beginning the
perimenopausal window.

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FSH &
LH
IU/L

100

90

80

70

60
Estradiol
Estrone pg/mL
50
200

40
160

Estradiol

30
120

Estrone
20
BO

10
40

The Perimenopausal Transition (mean circulating hormone levels)

FSH

LH

0
0

44
46
18
50
52
54
56
58

Age (years)

Menopause

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The Perimenopausal
Transition
•Average age of onset
Age of onset for 95% of women
Average duration
•Duration for 95% of women
46

39-51
5 year
2-8 year

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Premenopause

Premenopause is a word used to describe

the years leading up to the last period, when
the levels of reproductive hormones are
already becoming lower and more erratic,
and the effects of hormone withdrawal may
be present.
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Postmenopause

Postmenopause is all of the time in a

woman's life that take place after her
last period, or more accurately, all of
the time that follows the point when
her ovaries become inactive.

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Peri menopause

5 years
Senilis
Post menopause
Fertil
11-2 years

Pre menopause
1-2 years

Menopause

(no periods in 12 months)

2

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The age of menopause

☐ Median age
50 and 52

No corelation between age of menarche and

age
of menopause
Earlier menopause:
Smoking
Thin women
Women undergone abdominal hystercetomy or endometrial ablation
Nullipara

Later menopause:
Consumption alcohol
Obese

Multi parity

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GnRH
Progesterone 17-0HP Ng/mL
PHYSIOLOGY OF OVULATION/MENSTRUATION

10
GONADOTROPIN
9

LH
Progesterone
8
LH
FSH
7
FSH

6
Estradiol

Estradiol
2

1
Estradiol
17-OH Progesterone
17-OH Progesterone

ESTROGEN
Progesterone

&
Ov.
24
6 8 10 12
14
16
18 20 22 24
26 28

PROGESTERON
Cy

ENDOMETRIUM
FSH
LH

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Actions of Estrogen

□ Development of ovaries, tubes,

uterus and vagina
Secondary sexual characteristics
HPO axis interaction
Proliferative changes in the
endometrium

Increases fat deposition and vascular

profusion of
skin

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Specific
Actions of Progesterone
Interacts with hypothalmus and
pituitary to regulate
menstrual cycle
Produces secretory changes in the
endometrium
Increases viscosity of cervical mucus
Prepares breast for lactation during
pregnancy

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PATHOPHYSIOLOGY

The number of primordial follicle decline

even before birth but dramatic just before
menopause.
Close to menopause, there will be:
-anovulation
-inadequate Luteal phase → decrease
progesterone
but not estrogen level → lead to AUB and
endometrial hyperplasia
□ At menopause dramatic decrease of
estrogen → menstruation ceases and
symptoms of menopause started.
But
still ovarian stroma androstenedione
postmenopausal
main
produce →small and testosterone, estrogen is
estrone produced by peripheral fat from
adrenal androgen
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HORMONE PRODUCTION AFTER MENOPAUSE

Shortly after menopause:

FSH increase 10-20 fold

LH increase 3 fold

Decrease Androstenedion

Decrease DHA and DHEAS

Decrease Testosteron

TAAL.FK
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THE IMPACT OF LOW

ESTROGEN

VASOMOTOR SYMPTOMS

ATROPHIC CHANGES

PSYCHOPHYSIOLOGIC EFFECTS

COGNITION AND ALZEIMER'S DISEASE

CARDIOVASCULAR DISEASE

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VASOMOTOR SYMPTOMS

THE

HOT
FLASH COOK
BOOK

Original Artist
Reproduction rights obtainable from www.CartoonStock com
ww
Search for doinst
HOT FLUSHES

Sudden onset of reddening of the skin

over the head, neck and chest,
accompanied by a feeling of intense
body heat and concluded by sometimes
perspiration

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VASOMOTOR SYMPTOMS
Who turned up the heat?
HOT FLUSHES
cutaneous vasodilation duration seconds
to several minutes (rarely hour)
Increase
10%
(premenopause) to 50%
(menopause)
more severe after surgical menopause
continue for 1 year
25% continue more than 5 years

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VASOMOTOR SYMPTOMS

Carol found her own way of coping with the hot flushes
ງ

MILK

HOT FLUSHES

☐ >> on overweight women

(effect of body fat causing a higher core
body temperature) can be secondary to
disease:
Pheochromocytoma
☐ Carcinoids

Leukimias

Pancreatic tumors

Thyroid abnormalities
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ATROPHIC CHANGES

Estrogen↓

Vagina loss colagen, adipose tissue, the

ability to retain water↓

Vaginal walls shrink, the rugae flatten and

disappear

Ratio superficial to basal cells

Vaginal surface friabel, prone to bleeding

with minimal trauma
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ATROPHIC CHANGES

pH vagina more alkaline (pH > 4.5)

Less lactobacillus
□ More susceptible to infection by
urogenital and fecal pathogens
Infecting organism can ascending
into urinary system to cause urethritis,
UTI, and cystitis
□ Dyspareunia → less complain →
sexual behaviour

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PSYCHOPHYSIOLOGIC
EFFECTS

Decreased level of central

neurotransmitters
□ Depression
Irritability
Anxiety
Insomnia
Loss of concentration

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CARDIOVASCULAR DISEASE
□ Reproductive year: risk coronary
heart disease (CHD) for women < men
☐ High HDL (estrogen and lower levels
testosteron)

After menopause: the risk CHD doubles

for women (total and LDL chol rise
rapidly after menopause)

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OSTEOPOROSIS
Characterized by low bone mass and
microarchitectural deterioration of bone
tissue, leading to enhanced bone fragility
and a consequent increase in the risk
of fracture even with litle or no trauma
Risk of fracture from osteoporosis will
depend on bone mass at the time of
menopause and the rate of bone loss
following menopause

Bone mass in the hip and vertebral bodies is

accumulated by late adolescent (age
18) → ceases around age 30

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Low calcium
Low vitamin D

Excess caffeine and low calciumi

Excess alcohol

Diet
Pathophysiologic

Race
Lack of estrogen
Body weight
Diseases

Osteoporosis
Singking

Heparin
Anticonvulsants
Thyroxine
Conicosteroids

Drugs

Environmental
factors
Sedentary

Lifestyle

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OSTEOPOROSIS - SIGNS &

SYMPTOMPS
Spinal (vertebral) compression fracture
☐ 50% of women over 65 year of age

Pain, loss of height, postural deformitiess

(the kyphotic
with consequent
dowarger's
hump)
gastrointestinal, bladder dysfunction
pulmonary,

The most common sites for vertebral fracture are 12 th

thoracic and the first 3 lumbar vertebrae.

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OSTEOPOROSIS-RISK FACTORS

☐ Old age
‫ם‬
Female sex

Previous history of fragility fracture Fractures, especially those

of the hip, spine, vertebrae, and wrist
☐ Family history of fragility fracture in close relative
☐ Smoking
Being thin and small frame

Family history of osteoporosis

Amenorrhea (hypoestrogenism) before menopause
Lifelong deficient calcium intake
Use of bone losing medications Sedentary lifestyle
。 Excessive use of alcohol

Loss of height (over 4 cm)

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OSTEOPOROSIS- Measuring
Bone Density

DEXA (Dual-energy X-ray

absorptiometry)
□ good precision for all side osteoporotic
fracture
□ less radiation than chest X ray
whole body scan can measure total body
calcium, lean body mass and fat mass
□ peripheral DEXA methods measure bone
density in the wrist, hell or finger
Screening: single source x-ray
absorptiometry on radius or calcaneus

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OSTEOPOROSIS- Measuring
Bone Density

The clinical relevance of bone density

measurement in post menopausal woman
are estimated by using T score (the more
negative, the greater the risk of fracture)

NORMAL

OSTEOPENIA

OSTEOPOROSIS
0 to 1 S.D from the reference standart (84% of the
population)
-1 to -2.5 S.D

Below -2.5 S.D

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OSTEOPOROSIS

HORMONAL THERAPY (HT)

Is effective in preventing the bone
loss associated with the menopause
Decrease the incidence of all
osteoporosis-related fracture, including
vertebral and hip fracture, even in patients
at low risk for fracture
Is indicated for the prevention of bone
loss in women with premature
menopause and secondary amenorrhea

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OSTEOPOROSIS
HORMONAL THERAPY (HT)

Is indicated in postmenopausal women in

the age group 50-60 year presenting with
a risk for fracture
Potential adverse effect of HT can be
limited by using lower than standart doses or
by avoiding oral adminstration, without
compromising the beneficial effect of HT on
bone

The protective effect of HT on bone

mineral density is lost after cessation of
therapy at unpredictable rate.

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OSTEOPOROSIS
Non-hormonal therapy
□ Calcium and vit D: is able to reduce the risk of
falling, and decrease the hip fracture risk, provided
the dose of vit D at least 1200 IU/d

☐ Exercise: Postmenopausal women

engaging in aerobic
exercise training, resistance training, or both
combinations
Biphosphonate: bone turn over normalizes within
weeks and no further suppresion is seen during
long-term use with up to 10 years. of continuing
administration.
Both vertebral and non vertebral antifracture efficacies are
detectable after 6 months of treatment

The antifracture efficacy seem to last more than 5

years after cessation of treatment

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Table 4 Antiosteoporotic medications available in Taiwan and their clinical evidence.
Medications
Frequency
Indications

osteoporosis
Vertebral Nonvertebral Osteoporosis Glucocorticoid-induced Primary
fracture fracture
in men
Osteoporosis
fracture prevention*
prevention

Bisphosphonates
Alendronate
Weekly
++
++
++
++
++
++
Risedronate
Weekly/monthly ++
++
++
++
++
++
Zoledronate
Annually
++
++
++
++
++
++
Ibandronate
Every 3 months ++
+
+
N/A
N/A
N/A
Anti-RANKL monoclonal antibody
Denosumab Every 6 months ++
++
++
++
+
N/A
Estrogens, SERMS and STEAR
Estrogen
Daily
++
++
N/S
N/S
++
++
Raloxifene
Daily
++
+
N/S
N/A
++
++
Bazedoxifene
Daily
++
+
N/S
N/A
N/A
N/A
Tibolone
Daily
++
N/A
N/S
N/A
N/A
N/A
Vitamin D

12(OH)Dz/
Daily
+
N/A
N/A
N/A
N/A
1a,25(OH)2D
Parathyroid hormone preparations
Teriparatide Daily
++
++
++
++
N/A
N/A

Anti-sclerostin monoclonal antibody

Romosozumab Monthly
++
++
+
N/A
+
N/A

++: Adequate evidence supported. +: Partial evidence supported. N/A: No evidence

available. N/S: Not suitable *Primary fracture prevention for osteoporosis patients
without a history of fragility fractures.
In Taiwan, parathyroid hormones (1-84) and oral ibandronate are not available. The use
of calcitonin nasal spray for the treatment of osteoporosis was discontinued in 2013.
Strontium ranelate was taken off the market in 2018.
Abbreviations: RANKL, receptor activator of nuclear factor kappa-B ligand; SERM,
selective estrogen receptor modulator, STEAR, selective tissue estrogenic activity
regulator.

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Estrogen/Progesterone Therapy
Potential Risks and Concerns

Women's health initiative study

Breast cancer

□ Cardio vascular disease

Venous thrombosis Endometrial cancer

Compliance/therapy
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WHI Objective

Assess benefits and risks of the most commonly

used
E/P combination in the US
16,608 women randomized

8, 506 - E+P (.625 CEE + 2.5 MP)

8, 102 - placebo
Planned duration 8.5 years
Post menopausal women age 50-79 years

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LL

Women's Heath Initiative

Primary Conclusion

The risk-benefit profile found in this trial

is not consistent with the requirements
for a viable intervention for primary
prevention of
prevention of chronic diseases, and the
results indicate that this regiment should
not be initiated or continued for primary
prevention of CHD."

JAMA 2002;288:321-333
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AL
8

WHI
Implications/Limitations

Absolute risks -small

E/PT for treatment of menopausal symptoms

not evaluated
Only one drug used not comparable for
other E/PTS
 BALIFIC
E
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Summary (WHI Trials)

Breast CA
E/P

Significant increased risk

E/Only

Did not detect increased risk

Coronary heart
disease events
Significant increased risk
Did not detect
increased risk

Hip fractures
Decreased risk
Decreased risk

Colon cancer
Decreased risk
Decreased risk

Stroke
Increased risk
Increased risk

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