MenopauseMenopause

I. IntroductionI. Introduction - The term menopause is derived from Greek Meno - The term menopause is derived from Greek Meno

(months) and pause (cessation). The word means (months) and pause (cessation). The word means cessation of menstruation.cessation of menstruation.

- Cliamacteric which is by dictionary definition is - Cliamacteric which is by dictionary definition is period of life when fertility and sexual activity period of life when fertility and sexual activity decline. It is a wide term leading to:decline. It is a wide term leading to:

*Pre Menopause*Pre Menopause **Peri MenopausePeri Menopause *Post Menopause*Post Menopause

Perimenopause Definition:Perimenopause Definition:

- It is 3-5 years period before menopause with increase - It is 3-5 years period before menopause with increase frequent irregular anovulatory bleeding followed by frequent irregular anovulatory bleeding followed by episodes of ammenorrhea and intermittent episodes of ammenorrhea and intermittent menopausal symptoms.menopausal symptoms.

Menopause:Menopause: - - The point in time at which menstrual cycles The point in time at which menstrual cycles

permanently cease. It is a retrospective diagnosis permanently cease. It is a retrospective diagnosis after 12 months of ammenorrhea women classified as after 12 months of ammenorrhea women classified as being menopause.being menopause.

- Mean age – 51 years.- Mean age – 51 years.

II. PathophysiologyII. Pathophysiology The number of primordial follicle decline even before birth The number of primordial follicle decline even before birth

but dramatic just before menopause.but dramatic just before menopause. Increase FSH, LH from about 10 years before menopause.Increase FSH, LH from about 10 years before menopause. Close to menopause: There will beClose to menopause: There will be -anovulation-anovulation -inadequate Leuteal phase →-inadequate Leuteal phase → decrease progesterone but not astrogen level → lead todecrease progesterone but not astrogen level → lead to DUB and endometrial HyperplasiaDUB and endometrial Hyperplasia - at menopause dramatic decrease of astrogen→menstruation - at menopause dramatic decrease of astrogen→menstruation

ceases and symptoms of menopause started.ceases and symptoms of menopause started. But still ovarian stroma produce But still ovarian stroma produce →small androstenedione and →small androstenedione and

testosterone but, main postmenopausal astrogen is estrone testosterone but, main postmenopausal astrogen is estrone produced by Peripheral fat from adrenal androgen.produced by Peripheral fat from adrenal androgen.

III. Symptoms of Menopause:III. Symptoms of Menopause:1. Hot flushes cutaneous vasodilation1. Hot flushes cutaneous vasodilation - occurs in 75% of women- occurs in 75% of women - more severe after surgical menopause- more severe after surgical menopause - continue for 1 year- continue for 1 year - 25% continue more than 5 years- 25% continue more than 5 years

2. Urinary Symptoms2. Urinary Symptoms - urgency- urgency - frequency- frequency - nocturia- nocturia

3. Psychological changes decreased level of central neurotransmitters3. Psychological changes decreased level of central neurotransmitters - Depression- Depression - Irritability- Irritability - Anxiety- Anxiety - Insomia- Insomia - lose of concentration- lose of concentration

4. Atrophic Changes4. Atrophic Changes Vagina Vagina *vaginitis due to thinning of epithelium, ↓ PH and lubrication.*vaginitis due to thinning of epithelium, ↓ PH and lubrication. *dysparnue→due to decrease vascularity and dryness*dysparnue→due to decrease vascularity and dryness Decrease size of cervix and mucus with retract of segumocolumnar (SC) Decrease size of cervix and mucus with retract of segumocolumnar (SC)

junction into the endocervical canal.junction into the endocervical canal. Decrease size of the uterus, shrinking of myoma & adenomyosis.Decrease size of the uterus, shrinking of myoma & adenomyosis. Decrease size of ovaries, become non palpable.Decrease size of ovaries, become non palpable. Pelvic floor - relaxation Pelvic floor - relaxation →prolapse.→prolapse. Urinary tract →atrophy →lose of urethral tone →caruncleUrinary tract →atrophy →lose of urethral tone →caruncle

Hypertonic Bladder - detrusor instability Hypertonic Bladder - detrusor instability Decrease size of breast and benign cysts.Decrease size of breast and benign cysts.

5.5. Skin Collagen – Skin Collagen – ↓ collagen & ↓ collagen & thickness thickness →→ ↓↓ elasticity of the skin. elasticity of the skin.6.6. Reversl of premenstural syndromReversl of premenstural syndrom

IV. Late effect of MenopauseIV. Late effect of Menopause

A. Osteoporosis:A. Osteoporosis: - - bone mass reach peak at the end of their 3bone mass reach peak at the end of their 3 rdrd

decade of life.decade of life. - After 40years bone resorption exceeds bone - After 40years bone resorption exceeds bone formation by 0.5% per year.formation by 0.5% per year. - This negative balance increase after - This negative balance increase after menopause to a lose of 5% of bone permenopause to a lose of 5% of bone per year.year.

Risk factors:Risk factors:- Gender: more in women (male to female ratio is 1:3)Gender: more in women (male to female ratio is 1:3)- BMIBMI- Race Race *high in white women*high in white women *moderate in Asian women*moderate in Asian women *lowest in Black women*lowest in Black women- Family History +veFamily History +ve- Life styleLife style- smokingsmoking *caffeine intake*caffeine intake *alcohol*alcohol *increase in protein diet*increase in protein diet *decrease in Calcium and Vit D intake*decrease in Calcium and Vit D intake- Steriod Medication – Exogenous medicationSteriod Medication – Exogenous medication - Cushing Syndrome- Cushing Syndrome

Diagnosis – (DEXA-Daual Energy X-ray Absorptometry)Diagnosis – (DEXA-Daual Energy X-ray Absorptometry)-for Assessment of bone densmetry to demonstrate if bone -for Assessment of bone densmetry to demonstrate if bone desity above or below fracture threshold.desity above or below fracture threshold.

Prevention – improve lifestylePrevention – improve lifestyle - regular exercise- regular exercise - eliminate smoking & alcohol- eliminate smoking & alcohol MedicationMedication a. ERT (Estrogen Replacement Therapy)a. ERT (Estrogen Replacement Therapy) b. Biphosphonate (Fosamax) that inhibit b. Biphosphonate (Fosamax) that inhibit osteoclastic activity & minimal S/Eosteoclastic activity & minimal S/E c. Raloxifene (Evista) is selective oestrogen receptors c. Raloxifene (Evista) is selective oestrogen receptors moderator [SERMs] that bind with a high affinity to estrogen receptors. It moderator [SERMs] that bind with a high affinity to estrogen receptors. It

has some oestrogen like effect e.g. ↑ bone density, ↓LDL Cholesterol has some oestrogen like effect e.g. ↑ bone density, ↓LDL Cholesterol [cardioprotective] but act as estrogen antagonist on[cardioprotective] but act as estrogen antagonist on

endometriam and breast.endometriam and breast. d. Calcitonin inhibit osteoclastic activity + analgesic effect of d. Calcitonin inhibit osteoclastic activity + analgesic effect of e. Calcium Supplement & Vit D.e. Calcium Supplement & Vit D.

D. Cardiovascular DiseaseD. Cardiovascular Disease

CVD is now the leading cause of death among post CVD is now the leading cause of death among post menopausal womenmenopausal women

-before menopause, risk of heart attack is 1/3 of man-before menopause, risk of heart attack is 1/3 of man -after menopause increase in women become the -after menopause increase in women become the

same of man at an age of 70yearssame of man at an age of 70years Because of effect of oestrogen:Because of effect of oestrogen: **Before menopause:Before menopause: increase HDL & decrease increase HDL & decrease LDL.LDL. *decrease Atherogenic plague formation by direct *decrease Atherogenic plague formation by direct

action on vascular endonelium.action on vascular endonelium.

After menopause:After menopause:

--HDL : LDL ratio become closer to male ratio.HDL : LDL ratio become closer to male ratio.

--Observational StudiesObservational Studies

*HRT decrease mortality by 30%. But recent *HRT decrease mortality by 30%. But recent epidomalogical studies do not show a epidomalogical studies do not show a beneficial effect of HRT on CHD but there is beneficial effect of HRT on CHD but there is increase number of Breast Cancer when increase number of Breast Cancer when compared with non users HRT.compared with non users HRT.

E. Urogenital SystemE. Urogenital System Embryologically female genital tract & lower urinary system Embryologically female genital tract & lower urinary system

develop in close proximity from primitive urogenital sinus.develop in close proximity from primitive urogenital sinus. The Urethra and vagina have a high concentration of estrogen The Urethra and vagina have a high concentration of estrogen

receptors and there is significant evidence to support one use receptors and there is significant evidence to support one use of estrogen in treatment of urogenital symptoms such as of estrogen in treatment of urogenital symptoms such as (recurrent UTI, vaginitis ad dysparunia).(recurrent UTI, vaginitis ad dysparunia).

AL Zheimer’s Disease AL Zheimer’s Disease -prevalence of Dementia as high 50% by age 85 years.-prevalence of Dementia as high 50% by age 85 years. -ALZheimer s disease account for 60-65% of cases.-ALZheimer s disease account for 60-65% of cases. -observation studies –decrease risk of Al Zheimer’s by 1/3 -observation studies –decrease risk of Al Zheimer’s by 1/3

among women taking HRT.among women taking HRT. -it has beneficial effect on brain function but no randomized -it has beneficial effect on brain function but no randomized

studies to confirm observational data.studies to confirm observational data.

Diagnosis and Investigations:Diagnosis and Investigations: The Triad of:The Triad of: -Hot flushes-Hot flushes -Amenorrhea-Amenorrhea -increase FSH > 15 i.u./L-increase FSH > 15 i.u./L Before starting treatment: You should performBefore starting treatment: You should perform -breast self examination-breast self examination -mammogram-mammogram -pelvic exam (Pap Smear)-pelvic exam (Pap Smear) -weight, Blood pressure-weight, Blood pressure No indication to performNo indication to perform -bone density -bone density -Endometrial Biopsy -Endometrial Biopsy but any bleeding should be investigated before starting anybut any bleeding should be investigated before starting any treatment.treatment.

Treatment:Treatment: Estrogen – a minimum of 2mg of oestradiol is needed to Estrogen – a minimum of 2mg of oestradiol is needed to

mentain bone mass and relief symptoms of menopause.mentain bone mass and relief symptoms of menopause. Women with uterus – add progestin at last 10 days to prevent Women with uterus – add progestin at last 10 days to prevent

endometrial Hyperplasticendometrial Hyperplastic Sequential Regimens - used in patient close to menopause. Sequential Regimens - used in patient close to menopause. Oestrogen – in the first ½ of 28 day per packOestrogen – in the first ½ of 28 day per pack & Oestrogen & Progetin in 2& Oestrogen & Progetin in 2ndnd 1/12 of 28 day pack. 1/12 of 28 day pack. Combined continuous therapy who has Progesterone everyday Combined continuous therapy who has Progesterone everyday

– is useful for women who are few years past the menopause – is useful for women who are few years past the menopause and who do not to have vaginal bleeding.and who do not to have vaginal bleeding.

There is evidence that increase risk of endometrial cancer with There is evidence that increase risk of endometrial cancer with sequential regimens for > 5 years while on combined sequential regimens for > 5 years while on combined continuous regimens decrease risk of Cancer.continuous regimens decrease risk of Cancer.

Benefits of HRT:

Vagina-↑ vaginal thickness of epithelium →↓ Vagina-↑ vaginal thickness of epithelium →↓ dysparunia & vaginitis.dysparunia & vaginitis.

Urinary tract – enhancing normal bladder Urinary tract – enhancing normal bladder function.function.

Osteoporosis – decrease fractures by more Osteoporosis – decrease fractures by more than 50%than 50%

CVS – decrease by 30% by observation CVS – decrease by 30% by observation studies but recent studies shows no benefits.studies but recent studies shows no benefits.

Colon Cancer decrease up to 50%Colon Cancer decrease up to 50%

Confirmed Risk:Confirmed Risk: Endometrial CA eliminated byEndometrial CA eliminated by 1. Add Progesterone 1. Add Progesterone 2. Using selective oestrogen receptors modulators (SERMS).2. Using selective oestrogen receptors modulators (SERMS). Gall Bladder DiseaseGall Bladder Disease -ERT:-ERT: *↑ triglyceride*↑ triglyceride *↑total cholesterol*↑total cholesterol *increase risk of Gall stone*increase risk of Gall stone Breast Cancer risk with long term HRT addsBreast Cancer risk with long term HRT adds -2/1000 after 5 years – 6/1000 – 10years-2/1000 after 5 years – 6/1000 – 10years -12/1000 after 15 years – background risk 45/1000 betweenthe -12/1000 after 15 years – background risk 45/1000 betweenthe

age of 50 and 70 nott taken HRTage of 50 and 70 nott taken HRT

Contraindication to HRTContraindication to HRT

Undiagnosed vaginal bleedingUndiagnosed vaginal bleeding Acute liver disease.Acute liver disease.

-chronic impaired liver functions-chronic impaired liver functions Acute vascular thrombosisAcute vascular thrombosis Breast CancerBreast Cancer

Upper Reproductive Tract Causes:Upper Reproductive Tract Causes:

Atrophic EndometritisAtrophic Endometritis Endometrial PolypEndometrial Polyp Endometrial HyperplasiaEndometrial Hyperplasia Endometrial CaEndometrial Ca

Diagnosis:Diagnosis:

GIT AitologyGIT Aitology -rectal exam-rectal exam -stool for occult blood-stool for occult blood -Proctosigmoidoscopy-Proctosigmoidoscopy Lower Reproductive Tract Causes – can be Lower Reproductive Tract Causes – can be

identified by:identified by: *Pelvic Exam*Pelvic Exam *Pap Smear & appropriate Biopsy*Pap Smear & appropriate Biopsy

Upper Reproductive Tract Causes Can be Upper Reproductive Tract Causes Can be Identified only by: Tissue Diagnosis Obtained Identified only by: Tissue Diagnosis Obtained

by Endometrial Evaluationby Endometrial Evaluation1. 1. Endometrial Biopsy butEndometrial Biopsy but -helpful only if tre. biopsy inaccurate for diagnosis of Polyp & miss a sufficient -helpful only if tre. biopsy inaccurate for diagnosis of Polyp & miss a sufficient

number of hyperplasia.number of hyperplasia.2.2. Hysterosonography is performed by infusion saline in the uterine cavity to Hysterosonography is performed by infusion saline in the uterine cavity to

identify endomterial polyps.identify endomterial polyps. Endometrial thickness <10mm indicate risk of hyperplasia→tissue should Endometrial thickness <10mm indicate risk of hyperplasia→tissue should

be obtained for histological studies.be obtained for histological studies.3.3. Fractional dilation and curettage (D&C) is the good standard for evaluating Fractional dilation and curettage (D&C) is the good standard for evaluating

post menopausal bleeding. It is performed in 2 stage:post menopausal bleeding. It is performed in 2 stage: A. Initially endocervical canal is curretted obtaining the first specimen to A. Initially endocervical canal is curretted obtaining the first specimen to

rule out invasion of Cervix by Ca. rule out invasion of Cervix by Ca. B. Then uterine cavity is curreted obtaining second specimen to assess B. Then uterine cavity is curreted obtaining second specimen to assess

endometrial neoplasia or malignancy.endometrial neoplasia or malignancy.4. Hysteroscopy performed at the time of D&C for Polyp & operative 4. Hysteroscopy performed at the time of D&C for Polyp & operative

resection.resection.5. Pap Smear have poor sensitivity for endometrial cancer. only 40% cases 5. Pap Smear have poor sensitivity for endometrial cancer. only 40% cases

are identified.are identified.

Post Menopausal Bleeding:Post Menopausal Bleeding:

Vaginal bleeding occurs after 12months of Vaginal bleeding occurs after 12months of Amenorrhea in middle age women who are not Amenorrhea in middle age women who are not receiving replacement therapy. It can never be receiving replacement therapy. It can never be dysfunctional or anovulatory in nature (with dysfunctional or anovulatory in nature (with lose of functional ovarian follicle bleeding lose of functional ovarian follicle bleeding from normal ovulatory cycle is impossible).from normal ovulatory cycle is impossible).

Causes:Causes: Endometrial Ca:Endometrial Ca: The most common Gynecological malignancy.The most common Gynecological malignancy. -Endometrial neoplasia can progress from simple hyperplasia to -Endometrial neoplasia can progress from simple hyperplasia to

investive Ca caused by unopposed oestrogen.investive Ca caused by unopposed oestrogen. The mechanism of many End. Ca. is prolonged oestrogen The mechanism of many End. Ca. is prolonged oestrogen

stimulation of the endometrium unopposed by progesterone. stimulation of the endometrium unopposed by progesterone. The source may be:The source may be:

a. Exogenous Estrogen (E2) (ERT)a. Exogenous Estrogen (E2) (ERT) b. Peripheral Aromatization of Androstendione to estrone –b. Peripheral Aromatization of Androstendione to estrone –

obesety or PCOobesety or PCO c. Estrogen (E2) producing tumor (like granuloza cell ovarian c. Estrogen (E2) producing tumor (like granuloza cell ovarian

tumour)tumour) d. Tamoxifen Stimulation of Endometriumd. Tamoxifen Stimulation of Endometrium

Risk Factors:Risk Factors:

No pregnancyNo pregnancy Prolonged Reproductive Life – late menopauseProlonged Reproductive Life – late menopause Unopposed estrogenUnopposed estrogen Triad of diabetes, hypertension & obesity Triad of diabetes, hypertension & obesity

Differential Diagnosis can originate Differential Diagnosis can originate from:from: Gastro intestinal (GI) tractGastro intestinal (GI) tract -Hemorhoids-Hemorhoids -anal fissures-anal fissures -colorectal cancer-colorectal cancer Lower Reproductive Tract Causes:Lower Reproductive Tract Causes: -Atrophic vaginitis-Atrophic vaginitis -vaginal fissures/tumors-vaginal fissures/tumors -vulvar lesion/tumors-vulvar lesion/tumors -cervical lesion/tumors-cervical lesion/tumors

Management:Management:

I. Endometrial Hyperplasia: I. Endometrial Hyperplasia: influenced by age, influenced by age, history, & fertility desire.history, & fertility desire.

A. A. Progestin TherapyProgestin Therapy -patient not cardidates for surgery-patient not cardidates for surgery -desire her fertility -desire her fertility For simple Hyperplasia (no atypia) medoxy For simple Hyperplasia (no atypia) medoxy

reducing progesterone for last 10days of regular reducing progesterone for last 10days of regular cycle – follow up biopsy in 3-6 months. cycle – follow up biopsy in 3-6 months.

For simple Hyperplasia with Atypia – lower rate of For simple Hyperplasia with Atypia – lower rate of response to Progestin. Follow up biopsy in 3/12.response to Progestin. Follow up biopsy in 3/12.

B.B. Surgical Treatment Indicated forSurgical Treatment Indicated for:: Premenopausal hyperplasia with atypia and not desire preservation of her Premenopausal hyperplasia with atypia and not desire preservation of her

fertility or for post menopausal patient.fertility or for post menopausal patient. 1. Total Hysterectomy1. Total Hysterectomy a. abdomen – adhesiona. abdomen – adhesion b. vaginal – prolapseb. vaginal – prolapse

2. D&C – alone may on occasion be Therapeutic and Curative with on 2. D&C – alone may on occasion be Therapeutic and Curative with on further bleeding & normal histology on follow up biopsy.further bleeding & normal histology on follow up biopsy.

*Endometrial Cancer – management is primarily surgical with other *Endometrial Cancer – management is primarily surgical with other modalities as adjuvanits, depending on tumour grade & stage at modalities as adjuvanits, depending on tumour grade & stage at diagnosis.diagnosis.