Cagayan Valley Medical Center

DEPARTMENT OF OBSTETRICS AND GYNECOLOGY

MENOPAUSE

Cabaro, Sofia Kezia A. | SPUP Clerk | 6.4.21

 OUTLINE

I. Definition of Terms
II. Effects of menopause on
various organ system
III. Treatment

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 WHAT IS MENOPAUSE?

• Last menstrual period

• Average age: 51y/o
• Filipina: 47 & 48y/o
• Age of menopause is genetically determined.
Earlier Later No influence

Smoking Higher parity Physical /athletic activity

Higher altitude Higher BMI Education
Hysterectomy
Ethnicity

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 WHAT IS PERIMENOPAUSE?

• Variable time beginning a few years before and continuing after

the event of menopause.
• Most symptomatic phase for women.
• Rapid decline of primordial follicles reflected by ↓ AMH, and
ovarian inhibin B production accompanied by ↑ in FSH -
gametogenic ovarian failure.

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 WHAT IS PERIMENOPAUSE?

↓Ovarian capacity

↓ Inhibin B and AMH/MIS(<0.05ng/ml)

↑ FSH

↑ Activin (follicular atresia)

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 WHAT IS PERIMENOPAUSE?

• Clinical treatment of perimenopausal women should address three general

areas of concern:
(1) Irregular bleeding: OCP 20ug ethinyl estradiol
(2) Symptoms of early menopause, such as hot flushes: OCP
(3) Inability to conceive

Once day 3 FSH levels increase (>15 mIU/mL) Prognosis for pregnancy is
AMH levels decrease (≤0.4 ng/mL) markedly reduced!

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WHAT IS PERIMENOPAUSE?

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 KEYPOINTS

 Estradiol does not begin to significantly

diminish until approximately 1 year before
menopause. The rise in FSH occurs before this
and stabilizes about 2 years after menopause.

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 WHAT IS PREMATURE OVARIAN FAILURE?

 Defects
Defects in
in the
the X
X chromosome
chromosome

 Mutations in the gene encoding the FSH receptor
 Fragile X syndrome
• Hypergonadotropic ovarian failure 
 Type 1 blepharophimosis/ ptosis/epicanthus
inversus
inversus syndrome
syndrome

occurring prior to age 40. 



Triple X syndrome
Functional mutations in AMH
 Dystrophic
Dystrophic myotonia
myotonia
• Overall prevalence: 0.3 to 0.9%
• Causes:  Galactosemia

• Genetic
 17a-hydroxylase deficiency

• Enzymatic  Autoimmune polyendocrinopathy/c

andidiasis/ectodermal
andidiasis/ectodermal dystrophy
dystrophy (APECED)
(APECED)

• Immune  Ovarian
Ovarian autoantibodies/
autoantibodies/ autoimmunity
autoimmunity

• Gonadotropin effects  Abnormalities in the structure of gonadotropins

 Abnormalities of FSH receptor
• Ovarian insults
• Idiopathic 


Ionizing
Ionizing radiation
radiation (400,
Chemotherapy
(400, 500,
500, 800
800 rad)
Chemotherapy (cyclophosphamide)
rad)
(cyclophosphamide)

 Overly aggressive ovarian surgery

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 WHAT IS PREMATURE OVARIAN FAILURE?

• Management:
• Screening for autoimmune disorders and a karyotype
• Vaginal ultrasound
 Screen for thyroid, adrenal, & other autoimmune disorders
• Treatment of all cases: estrogen replacement
• If fertility is a concern,: oocyte donation

! Estrogen replacement in these young women with POI is extremely

important is that these young women are at substantial long-term risk
for osteoporosis and cardiovascular disease (CVD).

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EFFECTS OF MENOPAUSE ON
VARIOUS ORGAN SYSTEMS

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I. CENTRAL NERVOUS SYSTEM

• The brain is an active site for

estrogen action as well as estrogen
formation.

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I. CENTRAL NERVOUS SYSTEM – VASOMOTOR EPISODES

• The hallmark feature of declining estrogen

status in the brain is the hot
flush/vasomotor episode.
• “Hot flash” usually refers to the acute
sensation of heat.
• “Flush or vasomotor episode” includes
2 years after the onset of estrogen
changes in the early perception of this event
deficiency but can persist for 10
and other skin changes (including
or more years.
diaphoresis)

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I. CENTRAL NERVOUS SYSTEM – VASOMOTOR EPISODES

• Causes • Results – Heat Dissipation

• ↓Estrogen levels • ↑Peripheral temp
• Narrowed thermoneutral zone • ↓Skin resistance w/ diaphoresis
• Hypothalamic response to the • ↓Core body temp
change of estrogen status

 Sleep disruption

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I. CENTRAL NERVOUS SYSTEM – OTHER EFFECTS

• Depression (clinical or subclinical)

• Cognitive decline
• Timing of initiation of therapy is important

“while early treatment with estrogen in younger women at the

onset of menopause may be beneficial for cognition as it is with
certain types of mood, later treatment has no benefit and may even
be detrimental, depending on the regimen of hormones used.”

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II. COLLAGEN AND OTHER TISSUES

• Nearly 30% of skin collagen is lost within the first 5 years after menopause,
and collagen decreases approximately 2% per year for the first 10 years
after menopause.
• The supportive effect of estrogen on collagen has important implications
for bone homeostasis and for the pelvis after menopause.
• Symptoms of urinary incontinence and irritative bladder symptoms occur in
20%-40% of perimenopausal and postmenopausal women.

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III. VULVOVAGINAL ATROPHY

• During perimenopause, symptoms of  Thin, paler vaginal

dryness and atrophic changes occur in 21% mucosa
 Low moisture content
and 15% of women.  pH increases (>5)
 inflammation and
• Dyspareunia: 41% in 60y/o small petechiae

Estrogen treatment:
• Vaginal DHEA (0.25% to 1.0%)
• Ospenifene 60 mg
• Lubricants and moisturizers

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IV. BONE

• Estrogen deficiency has been well  ↑ remodeling units

 Prolongs resorption
established as a cause of bone loss.  Shortens bone
• Loss of trabecular bone (spine) is formation

greater with estrogen deficiency than is

loss of cortical bone.  Phase 1 - accelerated loss
cancellous bone
 Phase 2 – slower phase of
cortical bone loss

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 IV. BONE - DIAGNOSIS

• Dual-energy x-ray absorptiometry

(DEXA) scans have become the
standard of care for detection of
osteopenia and osteoporosis.

• Osteopenia: –1 to –2.5 sd

• Osteoporosis: >2.5 sd

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IV. BONE - MONITORING

• Biochemical assays

 Useful as markers of the

effectiveness of treatment

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IV. BONE - DIAGNOSIS

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IV. BONE - TREATMENT

• Estrogen - 0.625mg of CEE, 0.3mg + progetogens, calcium

• Selective estrogen receptor modulators (SERMs) - raloxifene,
droloxifene, and tamoxifen, Tibolone
• Bisphosphonates - etidronate, alendronate, risedronate,
ibandronate, and zoledronic acid
• Denosumab - 60 mg is SQ every 6 months
• Calcitonin - 50 IU SQ injections daily, or 200 IU intranasally
• Fluoride - (50 μg daily) of slow-release sodium fluoride
• Intermittent parathyroid hormone (PTH)
• Adjunctive measures – Calcium, Vitamin D and exercise

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 KEYPOINTS

 About 1% to 1.5% of bone mass is lost each year after

menopause in non-obese white and Asian women.

 Fractures begin to occur about age 60 to 65 in

trabecular bone, such as the vertebral spine, and by
age 60, 25% of these women develop spinal
compression fractures. Hip fractures begin to increase
after age 70.

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 KEYPOINTS

 Dual-energy x-ray absorptiometry (DEXA) is the most

accurate method to measure bone density.

 In addition to estrogen (with and without progestogen),

alendronate, risedronate, ibandronate, zoledronic acid,
raloxifene, calcitonin, denosumab, and teriparatide will
reduce postmenopausal bone loss, and some agents
will stimulate bone formation as well.

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V. CARDIOVASCULAR EFFECTS

• CVD risk ↑ - CAD is the leading cause of death in women

 Accelerated rise in total cholesterol – LDL
• Premature menopause & Oophorectomy - ↑ risk of MI
 ↓Prostacyclin
• Blood flow in all vascular beds ↓  ↑Endothelin
 Constrictive vasomotor response
• Carbohydrate tolerance ↓ due IR (↓NO)

• Biophysical and neurohormonal responses to stress (stress reactivity) are

exaggerated

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 V. CARDIOVASCULAR EFFECTS

 Protective effects of estrogen on the cardiovascular system led to the belief that
estrogen should be prescribed to prevent CVD in women.
 Young, healthy, symptomatic women
X women with established coronary disease

 Estrogen is what is protective, and Progestogens, depending on the type and

dose, are likely to attenuate or eliminate any protective effect and may be
implicated as well in the risk of breast cancer.

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V. CANCER RISK

• risk of cancer also increases with time after menopause, but

this is a function of aging and not as a consequence of
menopause per se.
• Lung CA > Breast CA
• Endometrial cancer - ↑unopposed estrogen therapy
• Breast cancer – dose and duration related
• Ovarian cancer
• Colorectal cancer

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DISEASE PREVENTION AFTER
MENOPAUSE
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HORMONE REGIMEN:
Estrogen

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HORMONE REGIMEN: • Equivalent doses to prevent
Progestogen
hyperplasia when administered for
at least 10 days in a woman
receiving ET:
• MPA, 5 mg;
• NET, 0.35 mg; and
• micronized progesterone, 200
mg.

The number of days (length of

exposure) is more important than the
dose!

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HORMONE REGIMEN:
Androgen Therapy

 Libido and energy

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ALTERNATIVE THERAPIES FOR MENOPAUSE

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 KEYPOINTS

 Onset of menopause heralds an important opportunity

to institute prevention strategies for prolonging and
improving the quality of life for women

 Estrogen is the best therapy for the hot flush; other

effective therapies are progestogens, selective
serotonin reuptake inhibitors (SSRIs), gabapentin,
clonidine, some phytoestrogens, acupuncture, and
stellate ganglion blockade.

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 KEYPOINTS

 The primary indication for estrogen therapy is

symptoms of menopause (hot flushes as well as
quality-of-life issues); bone health may also be an
indication in some women.

 In younger postmenopausal women who are receiving

hormonal therapy for symptoms, the benefits outweigh
risks with standard doses; lowering doses further
decreases risks.

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 KEYPOINTS

 There is no risk of coronary disease and possibly

some benefit with early treatment; there are small
risks of venous thrombosis and possibly of ischemic
stroke, which can be minimized or eliminated with
lower doses or transdermal therapy.

 There are consistent data for a reduction in all-cause

mortality of 20% to 30% in younger women who
initiate estrogen therapy at the onset of menopause.

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 KEYPOINTS

 Breast cancer risk is related to dose, duration of use,

and progestogen exposure. Estrogen alone and
possibly the use of natural progestogen do not
substantially increase the risk.

 There is no proved cognitive benefit (although this has

been shown in observational studies), but there is also
no evidence for harm if initiated in symptomatic
women at the onset of menopause.

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THANK YOU DOCTORS!