Professor Hassan Nasrat

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The Menopausal Woman
Professor Hassan Nasrat FRCS, FRCOG Professor
of Obstetrics and Gynecology Faculty of Medicine
King Abdulaziz University
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Definition and Terminology Pathphysiology Do we
have a real problem? Symptoms and Signs
(Consequences of E deprivation) Long Term Risk of
E deprivation Management HRT and The Controversy
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The Menopause and The Perimenopause

The Menopause Permanent cessation of
menstruation resulting from the loss of ovarian
follicles (WHO). Is a retrospective diagnosis.
Perimenopause Is the period of time when normal
women, usually in their forties, and usually
menstruating, experience symptoms of oestrogen
deficiency due to declining ovarian function (1-9
years) This group has been termed the Sandwich
generation caring for their immediate families,
aging parents as well as having career commitment.
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The Perimenopause

• Gametogenic failure followed by.
• Ovarian hormonal failure Cessation of Estrogen.
• The Biochemical markers are unreliable in
  diagnosis of the perimenopause because of
  irregularity hormonal levels.

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Ovarian gametogenic Failure

• Failure in quantity Accelerated Loss of
  Follicles Decreased Fertility
  Rate
• Failure in quality
• Embryonic chromosomal anomalies e.g. Trisomies.
• Increased spontaneous miscarriage

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Age In Years
The Relation Between Age and Follicular
Follicle Depletion Appears to Accelerate in the
Decade Preceding Menopause In the Menopause
There is Almost Complete Cesation of Ovarian
Estrogen production

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Changes in female life expectancy and age of
menopause
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Definition and Terminology Pathphysiology Do we
have a real problem? Symptoms and Signs
(Consequences of E deprivation) Long Term Risk of
E deprivation Management HRT and The Controversy
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Ovarian Hormonal Failure Cessation of Estrogen
Hormones

• Change in Menstrual Pattern
• Vasomotor instability
• Sleep Disturbances
• Psychological/cognitive disturbances
• Atrophic Conditions
• Somatic Symptoms
• Long-term problems 2ry to oestrogen deprivation

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Consequences Of Cessation Of Estrogen Production
Early Symptoms
Late Physical Changes
Later Diseases
Osteoporosis CVD Dementia (AD) Cancer
Hot Flushes Insomnia Irritability Mood
disturbances
Sexual Dysfunction Stress Urinary
Incontinence Connective Tissue Changes
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Symptoms Physical Changes of Estrogen Deficiency
Affect 70 of Women, Vary in Severity Is a Form
of Thermoregulatory Dysfunction Can Effectively
be Treated with Estrogen Cause Sleeplessness,
with Serious Mood Disturbance, Depression and
Irritability
Hot Flushes
Atrophy of vaginal Epithelium and Dryness
Pudendal Nerve Neuropathy Dyspareunia, Decreased
Sexual Desire and Arousal (decreased clitoral
sensitivity)
Sexual Dysfunction
Urinary Symptoms
Atrophy of urethral and Trigon epithelium
Reduced Collagen Contents of Skin (wrinkles) and
Bones
Connective Tissue Changes
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Osteoporosis
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Osteoporosis
a systemic skeletal disease characterized by
low bone mass and microarchitectural
deterioration with a consequent increase in bone
fragility with susceptibility to fracture
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Estrogen and The Skeletal System
With Acute Estrogen Deficiency After The
Menopause, There Is Accelerated Bone Loss Which
Mounts To About 1-1.5 Loss Of Total Bone
Mass/Year. For The First 20 Years After
Cessation Of Menses, Menopause Related Bone Loss
Results In 50 Reduction In Trabecular Bone And
30 Reduction In Cortical Bone.
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Normal..VS.Osteoporotic Bone
Normal iliac crest
Osteoporotic iliac crest
Osteoporosis is a systemic skeletal disease
characterized by low bone mass and
microarchitectural deterioration with a
consequent increase in bone fragility with
susceptibility to fracture
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Oestrogen and The Skeletal System
The Precise mechanism of action of Oestrogen on
the skeletal system is unknown. It seems to acts
at different sites - Increase efficiency of
calcium absorption (enhance availability of Vit.
D, 1,25 dihydroxy vit. D) - Direct action on
Osteoblasts - Through stimulation of estrogen
dependant growth factors. - Promote the
synthesis of Calcitonin.
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Oestrogen and The Skeletal System

• Osteoporosis is a major public health problem.

Vertebral 700,000 Proximal femur 300,000 Di
stal forearm 200,000 Other limb
sites 300,000 Total 1,500,000
Annual incidence of fracture in the USA due to
osteoporosis

• The life time risk of hip fracture in white women
  is 15. The combined risk of breast, uterine and
  ovarian cancer.
• Hip fracture is fatal in 20. Half the survivors
  are unable to walk.

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• Risk Factors for Osteoporosis

• Family history of osteoporosis.
• Early natural or surgical menopause.
• Previous fragility fracture.
• Smoking.
• Low body weight.
• Medical disorders (e.g thyroid disease) ,steroid
  therapy

Depending on clinical risk factors alone is
inadequate. 30 of women with no risk factors
have significant bone loss (Slemenda etal Ann
Inter Med, 1990, 11296-101)
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Pathophysiologic factors
Age
Oestrogen
Race
Wt
Diseases
Low Ca. Low Vit D Alcohol
Smoking Sedentary
Osteoporosis
Lifestyle
Diet
Drugs
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Oestrogen and The Skeletal System
Peak Bone Mass determined by Genetic
Non-genetic factors (nutrition, exercise, ..etc)
Rate of bone loss in later life aging,
lifestyle, the menopause, smoking..etc
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• Measurement of BMD

• Most commonly used
• - Dual-energy X-ray absorptiomery (DXA).
• - Quantitative computed tomography (QCT).
• - Single-photon absorptiometry (SPA)

• Newer Technique
• - Ultrasound attenuation and velocity.
• - Magnetic resonance imaging.

• Other techniques
• - Dual-photon absorptiometry (DPA)
• - Neutron activation analysis.
• - Radiogrammetry radiographic densitometry.

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Dual Energy X-ray absorptiometry DXA
- Is the gold standard for BMD measurement. The
technique depends on measuring the row bone
mineral content (BMC) in a clinically relevant
area of the skeleton e.g vertebra or hip (gm
ca). - The BMD is obtained by dividing the
BMC by the area scanned (gm Ca /CM2). - The
result is expressed as Z score SD from
patient age mean value. T score SD from adult
standard value.
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Osteoporosis
The diagnosis of osteoporosis is currently based
on bone mass measurement
T score lt 1 SD Normal T score gt1
SD Osteopaenia T score gt 2.5 SD Osteoporosis
WHO, 1994
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DEXA report
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BMD Measurement using U/S
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Oestrogen and the CVS

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Deaths from CHD
10,000
Number of deaths per 10,000
Women
Men
1000
100
10
40-
45-
50-
55-
60-
65-
70-
75-
80-
85
Age band (years)
Bush, 1990
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Cardiovascular protective Effect of Estrogen

• Action On Lipid Metabolism
• Reduction In LDL-C (10-20)
• Raise The HDL-C (10-30)

• Direct Indirect Vascular And Hemostatic Actions
  
• Augment Vasodilator And Antiplatelets
  Factors, Nitric Oxide And Prostacycline.
• Estrogen Has Antioxidant And Calcium
  Channel Blocking Properties.
• Direct Inotropic Action On The Heart.

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Management of the Menopause
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• History
• symptoms of Estrogen deficiency
• History of relevant medical or surgical
  conditions (e.g. diabetes, CVD, Thrombosis,
  Canceretc.) in patient and family.
• History of Relevant medications e.g. steroid.
• Family history of Cancer (breast or ovarian)
• Examination And Investigations
• General
• Local including Pap Smear
• BMD
• Mammography

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• Counseling and Advice
• Life Style (Diet, exerciseetc.)
• Medications
• HRT
• Calcium
• Vit. D
• SERM
• Other specific agents for osteoporosis

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Management of Early Consequences of Estrogen
Deficiency
Hot Flashes, Vaginal Dryness, Urinary Symptoms,
And Emotional Liability etc
Estrogen Is The Most Effective Treatment
Available For Relief Of Menopausal Symptoms
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Estrogen and Recurrent UTI The Effect of
Intravaginal Estriol Vs. Placebo on the Incidence
of UTI in Postmenopausal Women with Recurrent UTI
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Effect of HRT in Bone Mass
Randomized placebo-controlled, prospective study
over two years period Oral HRT patients
maintained bone mass while placebo-treated women
lost significant mas2.3 was seen when HRT was
withdrawn.
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Estrogen Replacement TherapyERT

• Type of Estrogen
• Route of Administration
• Combined Preparation HRT
• Duration of treatment
• Risks of HRT

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Estrogen Replacement Therapy ERT

Oral Oestrogen Transdermal Oestrogen Gel
Containing oestrogen Estrogen Implants Vaginal
Oestrogen
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Combined Preparation HRT

• In Women With Intact Uteri Progesterone
  Preparation Should be Added.
• It Has Virtually Eliminated The Risk Of
  Endometrial Cancer..

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Risks Associated with HRT
General and Metabolic Risks Venous
thrombosis gallbladder diseases liver
diseases. Endometrial Neoplasia Breast Cancer
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Breast Cancer Risk and HRT

• One women in 12 will get Br. Ca. i.e. is
  cumulative life time risk by age 85 ys.
• Substational proportion of this risk occur in
  later life.
• Between 30-50 the risk is 2 per 20 ys or 0.1
  per y. Between 50-70 ys. The annual risk is
  2/1000. Or 2 cumulative risk between 50-60 years
  (0.2 per annum)

Cumulative number of Deaths for 100 000 female
births, in England and Wales, 1995
The Obstetrician and Gynecologist, Vol.. 1,
October, 1999, No2
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Ostrogen Hormone and Breast Cancer
Analysis of world literature. Collaborative group
on hormonal factors in breast cancer, Lancet
3501997

• There is a small but significant increase in risk
  beyond 5 years of HRT use. The relative risk is
  about 1.3 at 15 years. (i.e. in the decade 50-60
  the HRT user for 5-15 years may be considered to
  have an annual risk of 1.3? 0.2 per annum of
  developing breast cancer).
• The risk persists for 5 years after the end of
  therapy but not beyond that.

The Obstetrician and Gynecologist, Vol. 1, 1999,
No2
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Selective Estrogen Receptors ModulatorsSERM
Are group of antiestrogens that
possess Oestrogen Agonistic activity at desired
targets on bone and on lipoproteins. And
Antagonistic action on the breast and the
endometrium
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Selective Estrogen Receptors ModulatorsSERM
Molecular structure of Raloxifene hydrochloride
The potential benefits of SERM drugs include
protection from four diseasesOsteoporosis,
coronary heart disease, endometrial and breast
cancer.