Menopause

Dr. Triono Adisuroso, SpOG, M.Med, M.Phil

Head of Dept. of Obstetrics and Gynaecology
Permata Cirebon Hospital
Faculty of Medicine
The University of Gunung JaE Cirebon
 ObjecEves

Understand reproducEve aging

Physiology
Stages
Understand the physiologic changes and symptoms
associated with menopause
Discuss treatment opEons for condiEons associated
with menopause
Dene Premature Ovarian Failure
 ReproducEve Aging

Decline in reproducEve potenEal

Puberty Peak reproducEon Decline in
ferElity AnovulaEon (menstrual irregularity)
Menopause
Due to ovarian aging (physiology)
Progresses with the decline in oocyte/
follicular pool
 Reproduc1ve Aging
Hormonal Changes
Hypothalmus

GnRH

FSH

Inhibin B
+

Normal Ovary
Ovary
 Reproduc1ve Aging
Hormonal Changes
Hypothalmus

GnRH

FSH

Estradiol / Inhibin B
+

Aging Ovary
Ovary
 Reproductive Aging
Hormonal Changes
 Reproduc1ve Aging
Hormonal Changes
Hypothalmus

GnRH

FSH

Estradiol / Inhibin B
+

Menopausal Ovary
Ovary
Stages of ReproducEve Aging
 ReproducEve Stage

Miscarriage Rate /
month

25%

12%
Pregnancy Rate /
month

20 30 37 40 45
Age in years
 Perimenopause

Follows period of declining ferElity
Precedes menopause
Characterized by
cycle irregularity (shortening then lengthening)
increasing symptoms
DuraEon 2 to 8 years (average 5 years)
 Diagnosis of Perimenopause

Clinical diagnosis based on menstrual

cycle pa[ern.
Early follicular phase FSH and symptoms
may help solidify diagnosis.
Rule out hypothyroidism, depression etc.
 Perimenopause Symptoms:
Highly Variable
Vasomotor instability (85%)
Sleep disturbances
Mood disturbances.
Soma?c symptoms:
Fa?gue, palpita?ons, headache, increased
migraine, breast pain and enlargement.
Oligo- Anovula?on
heavier or irregular cycles.

 Management of Perimenopause

Goals:
PaEent educaEon
PrevenEon of endometrial cancer
Individualized symptomaEc relief
Menstrual control
Minimizing hot ashes
Mood disturbances
 Management of Perimenopause

Symptom Menstrual Birth Endometrial

Relief Cycle Control Cancer
Control Prevention
Hormonal +++ +++ +++ +++
contraceptives
(oral or ring)
Cyclic progestin +/- +/- - ++
therapy
Progesterone - +/- +++ +++
IUD
EPT ++ - - +++
 Menopause

Marks the end of reproducEve life
CessaEon of menses for 12 months
Clinical diagnosis (not labs)
Result of egg depleEon and estrogen
producEon by the ovary due to.
Natural aging or surgery

 Menopause Facts

Average age at menopause: 51 years

(1% 40, 5% > age 55)
Factors impacEng age at menopause
Maternal age at menopause
Tobacco use
SES/EducaEon
Alcohol use
Body Mass Index
Factors that probably dont impact on age at menopause
OCP use
Parity
Race
Height

 Menopause
100
90
80
Age (years)

70
60
50
40
Age at menopause
30
20
10
0

1850 1940 2000

Date
*Projected es1mate.
Federal Interagency Forum on Aging-Related Sta1s1cs. Indicator 2: Life Expectancy. Available at:
hKp://www.agingstats.gov/tables%202001/tables-healthstatus.html. Accessed 1/3/02.
US Department of Health and Human Services. Healthy People 2010. Washington, DC: January
 Physical Changes

Vasomotor instability Brain

Eyes
Metabolic Changes Teeth
Coronary Artery Disease Vasomotor
Heart
Accelerated bone loss
Breast
Skin changes Colon
Urogenital
Urogenital atrophy tract
CogniEon (?) Skin

Libido (?) Bone

 Hot Flushes

Sudden onset of reddening of the skin over the head,

neck, and chest accompanied by a feeling of intense body
heat and someEmes concluded by profuse perspiraEon
Number 1 complaint to physicians
Few seconds to several minutes
Rare to recurrent every few minutes
Most severe at night and during Emes of stress
More common among overweight women
Usually last for 1-2 years
25% will last for more than 5 years
 Management of Hot Flushes

Set realisEc goals!

Lower the ambient temperature
Estrogen (80-95% reducEon)
AlternaEve therapies
High dose progesEns
Tibolone
SSRIs (ParoxeEne, FluoxeEne(+/-))
SNRI (Velafaxine (+/-))
GabapenEn
Clonidine (+/-)
 Effect of ERT and HRT on Number
of Hot Flushes Over 12 Weeks
12
Placebo
0.625 CEE
Adjusted Daily Mean

10
0.625 CEE/2.5 MPA
8
Number*

0
1 2 3 4 5 6 7 8 9 10 11 12
Week
Ecacy-evaluable popula1on included women who recorded taking study medica1on and had at least 7
moderate-to-severe ushes/day or at least 50 ushes per week at baseline.
*Adjusted for baseline. Mean hot ushes at baseline = 12.3 (range, 11.313.8).
Adapted from U1an WH, et al. Fer1l Steril. 2001;75:1065-79.
 Complementary Approaches
May be eecEve
Black Cohosh
Soy/Phytoestrogens
Vitamin E (1 hot ash per day less)
No evidence
Dong quai
Acupuncture
Yoga
Chinese herbs
Evening primrose
Ginseng
Kava
Red Clover Abstract
 Sleep and Mood Disturbances

Vasomotor episodes have an adverse impact on

quality of sleep
Sleep disturbances lead to a reduced ability to hand
problems and stresses
Women with a history of depression are at risk of
reoccurrence during menopause
HRT may provide addiEonal benet to anE-
depressants in the management of
postmenopausal depression
 Cognition

Lack of agreement on impact of menopause

on cogniEon
No clear evidence that HRT prevents
cogniEve aging or enhances cogniEve
funcEon
Vascular infarcts associated with estrogen
may worsen demenEa in women over 65
Metabolic Changes with
Menopause
 Mechanisms of Menopause-
Related Increases in Adiposity

Preferen1al
abdominal fat Increased
Hormonal
changes of the
accumula1on abdominal and
menopause intra-abdominal
transi1on adiposity
Increased fat
Altered accumula1on
energy
metabolism
 The Menopausal Metabolic Syndrome

n Lipid Triad
Hypertriglyceridemia
HDL Cholesterol
LDL Cholesterol

n AbnormaliEes in Insulin
Insulin resistance insulin secreEon
insulin eliminaEon Hyperinsulinemia
HT reduces onset of DM and improves insulin resistance

n Other Factors
SHBG
Endothelial dysfuncEon
blood pressure
visceral fat
PAI-1
uric acid
Cardiovascular Disease
 Annual Incidence of Myocardial
Infarction in Women and Men in the U.S.

500 Men
400 Women
No. 300
X 103 200
100
0
29-44 45-64 >65

Age, years
 Hormone Replacement Therapy
and CAHD

Secondary PrevenEon of CAHD

HERS (Heart and Estrogen/progesEn
Replacement Study)
No Benet

Primary PrevenEon of CAHD
WHI (Womens Health IniEaEve)
No Benet (PotenEal benet to women 50-59 and/or
within 2-3 years of the onset of menopause)
 PrevenEon of CAHD

In general HRT should not be conEnued or

started to prevent heart disease
Discuss other methods of CVD prevenEon:
Exercise
Diet
Smoking cessaEon
Cholesterol lowering medicines StaEns
Aspirin
Osteoporosis
 Pathogenesis of Estrogen
Deficiency and Bone Loss

Estrogen loss triggers increases

in IL-1, IL-6, and TNF.
Increased cytokines lead to increased
osteoclast development and lifespan.
Increased turnover of osteoblasts.
Impacts vitamin D metabolism
Impacts on renal and intesEnal handling of
calcium
 Spinal BMD by Age and
Menopausal Status

1.1
Perimenopausal
Menopausal for
1.0 4 Years
BMD (g/cm2)

Menopausal for
5-14 Years Menopausal
0.9 for 15 Years

0.8
50 55 60 65 70

Mean Age (years)

n = 1426.
Pouills JM, et al. J Bone Miner Res. 1994;9:311-5.
 Consequences of Osteoporosis

Spinal (vertebral)
compression fractures
Back pain
Loss of height and
mobility
Postural deformities
Colles (forearm)
fractures
Hip Fractures
Tooth loss
 When to Measure BMD in
Postmenopausal Women
One or more risk factors
Age > 65 Smoking cigare[es
Caucasian race Low body weight
Family history ETOH
History of fracture Immobility*
History of falls Poor nutriEon
Bad eyesight MedicaEons
DemenEa Certain medical
Early menopause condiEons
(<45)
 Prevention of Osteoporosis
Calcium
1500mg elemental Calcium daily
One serving of dairy=300mg
Supplements (citrate, carbonate)
Divided doses
With meals
Vitamin D supplementaEon Pharmacologic
Sunshine (generally not recommended)
400 IU/daily HRT
Weight bearing exercise Raloxifene
Smoking cessaEon Bisphosphonates
ModeraEon of alcohol intake
 Treatment of Osteoporosis
(for prevenEon of fractures)

First Line Agents

Bisphosphonates
Raloxifene
Second Line Agents
Human recombinant PTH
Nasal salmon calcitonin
HRT
Fall prevenEon strategies
Changes in the Urogenital
System
 Physiologic Changes in the
Urogenital System

Decrease in producEon of vaginal lubricaEng

uid
Loss of vaginal elasEcity and thickness of
epithelium (vaginal atrophy)
Development of uretheral caruncles
Mucosal thinning of urethra and bladder
Vaginal Atrophy
 Urogenital symptoms

Dysuria
Urgency
Treatment
Frequency 1) Vaginal estrogen
Recurrent UTIs (progestogen not
necessary)
Dysparunia
2) HRT *
Pruritus
Stenosis
 Hormone Replacement Therapy

Benets
Decrease hot ashes
Prevents/treats osteoporosis and hip and
vertebral fractures
Prevents/treats urogenital atrophy

 Hormone Replacement Therapy

Risks
Increased risk for venous thrombosis and
embolism (may be dependent on route of
administraEon)
Increased risk for breast cancer with
prolonged (>3-5yrs) use (EPT, not ET)
Increased risk for endometrial cancer with ET
(not EPT) (if uterus present)

 Hormone Replacement Therapy

Areas of concern
Possible increase in cardiac events in older
women started on EPT (not ET)
Probably increase in (ischemic) strokes in
older women started on HRT

 Hormone Replacement Therapy

Risks are dependent upon

Age (total mortality reduced by 30% if started at age <60)
Time since menopause
Age at menopause
DuraEon of therapy
Type of HT
Route of administraEon
Dose of HT

Benets are dependent on

Number of menopause related symptoms
 Hormone Therapy Guidelines

IndicaEon: estrogen deciency symptoms

Vasomotor symptoms
Hot ushes, night sweats
Disturbed sleep pa[erns
FaEgue, concentraEon, memory
GU atrophy
Bladder irritability, vaginal dryness, dyspareunia
Guiding principle
Minimum dose for shortest Eme required
Consider non-hormonal alternaEves
 Summary of Key Points

ReproducEve aging is due to a decline in

the number of ovarian follicles.
Menopause
Signals the end of the reproducEve years
Diagnosed clinically
Not a disease
Symptoms are due to estrogen deciency.
 Key Points
CAD
Rise in risk probably due to metabolic changes
HRT not indicated for prevenEon or treatment at this
Eme
Osteoporosis
Evaluate all postmenopausal women over 65 (earlier
screening recommended if they have one or more risk
factors)
PrevenEon: Calcium, Vitamin D, weight-bearing exercise,
smoking cessaEon
Primary treatment: Raloxifene, Bisphosphonates
 Key Points
Currently, the primary reason to prescribe
HRT in postmenopausal women is for the
relief of symptoms associated with estrogen
deciency.
 Premature Menopause
DeniEons:
Early: age 40-44
Premature: <40
Causes
Surgical removal of uterus
Surgical removal of ovaries
Premature ovarian failure
 Premature Ovarian Failure

Sex chromosome abnormaliEes (usually

involving the X Chromosome)
Fragile X premutaEon
Autoimmune
Chemotherapy/IrradiaEon
 EvaluaEon of Premature Ovarian
Failure

Karyotype (<30 years of age)

Assessment for Fragile X premutaEon
(number of CGG repeats)
Survey for other autoimmune diseases (such
as hypothyroidism, adrenal insuciency)
 Premature Ovarian Failure is
Dierent from Menopause

10-20% of women with POF with normal

karyotypes will ovulate again
5% spontaneous pregnancy rate
Not normal reproducEve aging
 Treatment of Premature
Menopause

Hormone replacement therapy!!!

Counseling
Oocyte donaEon
 HIV and Menopause

Mean age of menopause in HIV-infected women is 47-48 (not

adjusted for risk factors).
May be dicult to dierenEate HIV symptoms from
symptoms of menopause.
Further research needed on the addiEve eects of
menopause, HIV, and anE-retroviral therapies.
Further research need on depression during the menopause
transiEon in HIV aected women.
Safety of HRT in HIV+ postmenopausal women has not been
studied.
Conde et al. Menopause 2009;16:199-213
Thank you