Professor Hassan Nasrat FRCS, FRCOG Professor of Obstetrics and Gynecology Faculty of Medicine
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Transcript of Professor Hassan Nasrat FRCS, FRCOG Professor of Obstetrics and Gynecology Faculty of Medicine
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Professor Hassan Nasrat FRCS, FRCOG
Professor of Obstetrics and GynecologyFaculty of Medicine
King Abdulaziz University
The Menopausal Woman
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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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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
Age In Years
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Changes in female life expectancy and age of menopause
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Definition and TerminologyPathphysiologyDo we have a real problem?Symptoms and Signs (Consequences of E deprivation)Long Term Risk of E deprivationManagement 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
Hot Flushes
Insomnia
Irritability
Mood disturbances
Sexual Dysfunction
Stress Urinary Incontinence
Connective Tissue Changes
Osteoporosis
CVD
Dementia (AD)
Cancer
Early Symptoms
Late Physical Changes
Later Diseases
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Symptoms & Physical Changes of Estrogen Deficiency
Urinary Symptoms
Affect 70 % of Women, Vary in SeverityIs a Form of Thermoregulatory DysfunctionCan Effectively be Treated with Estrogen Cause Sleeplessness, with Serious Mood
Disturbance, Depression and Irritability
Hot Flushes
Sexual Dysfunction
Atrophy of vaginal Epithelium and Dryness Pudendal Nerve Neuropathy
Dyspareunia, Decreased Sexual Desire and Arousal (decreased clitoral sensitivity)
Connective Tissue Changes Reduced Collagen Contents of
Skin (wrinkles) and Bones
Atrophy of urethral and Trigon epithelium
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Osteoporosis
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‘a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration with a consequent increase in
bone fragility with susceptibility to fracture’
Osteoporosis
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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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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’
Normal…..VS.…Osteoporotic Bone
Normal iliac crest Osteoporotic iliac crest
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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 700,000Proximal femur 300,000Distal forearm 200,000Other limb sites 300,000Total 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, 112:96-101)
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Pathophysiologic factors
Age Race Oestrogen Wt Diseases
Diet Drugs Lifestyle
Low Ca.
Low Vit D
Alcohol
Smoking
SedentaryOsteoporosis
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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 < 1 SD Normal
T score >1 SD Osteopaenia
T score > 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 Number of deaths per 10,000
Age band (years) Bush, 1990
1000
10,000
100
1040- 45- 50- 55- 60- 65- 70- 75- 80- 85+
Women
Men
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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, 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
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• Counseling and Advice:–Life Style (Diet, exercise…etc.)
• Medications: –HRT–Calcium –Vit. D–SERM–Other specific agents for
osteoporosis
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Hot Flashes, Vaginal Dryness, Urinary
Symptoms, And Emotional Liability… etc
Management of Early Consequences of Estrogen Deficiency:
Estrogen Is The Most Effective
Treatment Available For Relief Of
Menopausal Symptoms
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Estrogen and Recurrent UTIThe Effect of Intravaginal Estriol Vs. Placebo on the Incidence
of UTI in Postmenopausal Women with Recurrent UTI
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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.
Effect of HRT in Bone Mass
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Estrogen Replacement Therapy“ERT”
•Type of Estrogen:
•Route of Administration:
•Combined Preparation “HRT”
•Duration of treatment:
•Risks of HRT
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Oral Oestrogen
Transdermal Oestrogen
Gel Containing oestrogen
Estrogen Implants
Vaginal Oestrogen
Estrogen Replacement Therapy ’ERT’
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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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Cumulative number of Deaths for 100 000 female births, in England and Wales, 1995
•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)
Breast Cancer Risk and HRT
‘The Obstetrician and Gynecologist, Vol.. 1, October, 1999, No2’
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Ostrogen Hormone and Breast Cancer
•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.
Analysis of world literature. Collaborative group on hormonal factors in breast cancer, Lancet 350:1997
The Obstetrician and Gynecologist, Vol. 1, 1999, No2
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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
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Selective Estrogen Receptors Modulators‘SERM’
Molecular structure ofRaloxifene hydrochloride
The potential benefits of SERM drugs include protection from four diseases:Osteoporosis, coronary heart disease, endometrial and breast cancer.