Download Symptoms and Signs (Consequences of E deprivation)

The Menopausal Woman
Professor Hassan Nasrat
FRCS, FRCOG
Professor of Obstetrics and Gynecology
Faculty of Medicine
King Abdulaziz University
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
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
women,
usually in their forties,
menstruating, experience symptoms
deficiency due to declining ovarian
years)
when normal
and usually
of oestrogen
function (1-9
This group has been termed the “Sandwich generation” caring for their
immediate families, aging parents as well as having career commitment.
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.
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
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
Changes in female life expectancy and age of
menopause
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
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:
Consequences Of Cessation Of Estrogen Production
Early
Symptoms
Hot Flushes
Insomnia
Irritability
Mood
disturbances
Late
Physical Changes
Sexual
Dysfunction
Stress Urinary
Incontinence
Connective
Tissue Changes
Later
Diseases
Osteoporosis
CVD
Dementia (AD)
Cancer
Symptoms & Physical Changes of Estrogen Deficiency
Hot Flushes
Sexual
Dysfunction
Urinary
Symptoms
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
Atrophy of vaginal Epithelium and Dryness
Pudendal Nerve Neuropathy
Dyspareunia, Decreased Sexual Desire and
Arousal (decreased clitoral sensitivity)
Atrophy of urethral and Trigon epithelium
Connective Tissue Changes
Reduced Collagen Contents of
Skin (wrinkles) and Bones
Osteoporosis
Osteoporosis
‘a systemic skeletal disease characterized by
low bone mass and microarchitectural
deterioration with a consequent increase in
bone fragility with susceptibility to fracture’
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.
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’
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.
Oestrogen and The Skeletal System:
 Osteoporosis is a major public health problem.
Vertebral
Proximal femur
Distal forearm
Other limb sites
Total
700,000
300,000
200,000
300,000
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.
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, 112:96-101)
Pathophysiologic
factors
Age
Race
Oestrogen
Low Ca.
Osteoporosis
Low Vit D
Wt
Diseases
Smoking
Sedentary
Alcohol
Diet
Drugs
Lifestyle
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
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.
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.
Osteoporosis:
The diagnosis of osteoporosis is currently
based on bone mass measurement:
T score < 1 SD
Normal
T score >1 SD
Osteopaenia
T score > 2.5 SD
Osteoporosis
WHO, 1994
DEXA report:
BMD Measurement using U/S
Oestrogen and the CVS
Deaths from CHD
Number 10,000
of deaths
per
10,000
1000
Women
Men
100
10
40- 45- 50- 55- 60- 65- 70- 75- 80- 85+
Age band (years)
Bush, 1990
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.
Management of the Menopause
• History:
– symptoms of Estrogen deficiency
– History of relevant medical or surgical
conditions (e.g. diabetes, CVD, Thrombosis,
Cancer…etc.) 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
• Counseling and Advice:
–Life Style (Diet, exercise…etc.)
• Medications:
–HRT
–Calcium
–Vit. D
–SERM
–Other specific agents for
osteoporosis
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
Estrogen and Recurrent UTI
The Effect of Intravaginal Estriol Vs. Placebo on the Incidence
of UTI in Postmenopausal Women with Recurrent UTI
Effect of HRT in Bone Mass
Randomized placebo-controlled, prospective study over two years
period
Oral HRT patients maintained bone mass while placebotreated women lost significant mas2.3% was seen when HRT was
withdrawn.
Estrogen Replacement Therapy
“ERT”
•Type of Estrogen:
•Route of Administration:
•Combined Preparation “HRT”
•Duration of treatment:
•Risks of HRT
Estrogen Replacement Therapy ’ERT’
Oral Oestrogen
Transdermal Oestrogen
Gel Containing oestrogen
Estrogen Implants
Vaginal Oestrogen
Combined Preparation
“HRT”
- In Women With Intact Uteri Progesterone Preparation
Should be Added.
- It Has Virtually Eliminated The Risk Of Endometrial
Cancer..
Risks Associated with HRT:
General and Metabolic Risks:
Venous thrombosis
gallbladder diseases
liver diseases.
Endometrial Neoplasia:
Breast Cancer:
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 5060 years (0.2% per annum)
Cumulative number of Deaths for 100
‘The Obstetrician and Gynecologist,
Vol.. 1, October, 1999, No2’
000 female births, in England and
Wales, 1995
Ostrogen Hormone and Breast Cancer
Analysis of world literature. Collaborative group on
hormonal factors in breast cancer, Lancet 350:1997
•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
Selective Estrogen Receptors
Modulators
‘SERM’
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
Selective Estrogen Receptors Modulators
‘SERM’
Molecular structure of
Raloxifene hydrochloride
The potential benefits of SERM drugs include
protection from four diseases:Osteoporosis, coronary
heart disease, endometrial and breast cancer.