Menopause ppt

Preview:

Citation preview

Keerthi NS

2010 Batch

TMC Kollam

Menopause and its complications

1

2

• PERIMENOPAUSE– A period of 3years before menopause

& followed by 1 year of amenorrhoea– Assosiated with mild ovarian

hormonal deficiency – Leads to anovulation, menorrhagia

3

• MENOPAUSE– The time of cessation of ovarian

function resulting in permenant amenorrhoea

– For confirmation: 12 months• CLIMACTERIC:

– Phase of waning ovarian activity– 2-3yrs before and 2-5 yrs after

menopause

4

Demography; Indian perspective

• 60 million women in India are above 55yrs• Majority of women spend 1/3rd of their life in

postmenopausal period

5

Age • Usual age 45 to 50yrs average being 47yrs.• Premature menopause - before 40 yrs• Late menopause – menstruation beyond

52 yrs

6

• Delayed menopause– Due to good health and better nutrition.– Also seen in women with uterine fibroids .– Also in women with high risk of endometrial

cancer

• Menopausal age is directly associated with smoking and genetic disposition.

• Smoking induces premature menopause.

7

Pathophysiology

• During climacteric, ovarian activity declines.• Initially, ovulation fails, no corpus luteum forms

and no progesterone is secreted by the ovary.• Later, graffian follicle fails to develop,

estrogenic activity decreases and endometrial atrophy leading to amenorrhea.

• Increased secretion of FSH and LH by anterior pituitary.

8

9

• FSH 50 times increase, LH 3-4 times increase.

• Menopausal urine has become and important commercial source of gonadotropins.

Later gonadotropin activity of anterior pituitary ceases and fall in FSH level eventually occurs.

10

11

• Hormone levels

• 50% reduction in androgen production and 66% reduction in oestrogen production..

• Some estrogen produced by ovary (oestrone, E1)

• FSH appears in large concentrations.• Low oestrogen levels(below 20pg/ml)

predisposes to osteoporosis and ischemic heart disease.

13

Risk factors for menopausal related problems are as follows:

• Early menopause• Surgical menopause or radiation.• Chemotherapy esp alkylating agents.• smoking., caffeine, alcohol.• Family history of menopausal diseases. • Drugs related such as GnRH, heparin,

corticosteroids and clomiphene(anti- oestrogen) when given over prolonged peiod can cause oestrogen deficiency.

14

• Anatomical changesSITE CHANGES

Genital organs Atrophy and regression

Ovary Shrink,surfaces:grooved , furrowed

Tunica albuginea Thickens

Size of ovary <2*1.5*1cm in US

Plain muscle in fallopian tube:

Atrophy

Cilia Disappear

Uterus Smaller

Endometrium As basal layer: deeply stained stroma and a few glands

15

SITE CHANGES

Cervix Smaller

Vaginal fornices Disappears

Vagina Narrow

Epithelium Pale, thin,and dry: senile vaginitis

Vulva Atrophy (+narrow vagina:dyspareunia)

Skin of labia minora and vestibule Pale,thin,dry

Labia majora Reduction in fat

Pubic hair Reduced and grey

Breast More pendulous(fat dep)

Glandular tissue <5%

Pelvic cellular tissue Becomes lax

Ligaments supporting the uterus and vagina

Lose their tone:prolapse of genital organs, stress incontinence of urine, and fecal incontinence

16

Menopausal symptoms

• Mensural symptoms• Other symptoms• Neurological• Libido• Urinary tract• Genital

17

Menopausal symptoms

• Menstrual – 3 classic ways in which the menstrual period

ceases are as follows:• Sudden cessation.• Gradual diminution in the amount of blood loss

with each regular period until menstruation stops.

• Gradual increase in spacing of periods until they cease for at least a period of one year.

18

Other symptoms

• 60-70% women go through menopausal period without problems

• Rest needs guidance and treatment

19

Hot Flushes

• Early and acute symptom of estrogen deficiency.• These are waves of vasodilatation affecting the face

and neck and last for 2-5 mins each.• Followed by severe sweating.• Occurring at night may disturb sleep.• Sometimes preceded by headache.• Palpitation and anginal pain maybe felt.• Mental depression due to lack of sleep, irritability and

lack of concentration.• With passage of time severity of hot flushes

decreases. 20

Cause of hot flushes• Caused by noradrenalin, which disturbs the

thermoregulatory system.

• Oestrogen deficiency reduces hypothalamic endorphins, which release more norepinephrine and serotonin.

• This leads to inappropriate heat loss mechanism.

21

Neurological

• Vasomotor symptoms and paraesthesia take the form of sensations of pins and needles in the extremities.

22

Libido

• E and androgen deficiency causes urogenital atrophy,

which affect sexual function.

• Leads to a decline in sexual interest.

23

• The symptoms which develop a little later are :– Urinary

• Dysuria• Stress incontinence and urge• Recurrent infection

Genital Dry vaginaDyspareuniaLoss of libido

Faecal incontinence24

Urinary tract• Oestrogen deficiency

causes

• Urethral caruncle• Dysuria with or without

infection• Urge

• Stress incontinence( due to poor vascularity and loss of tone of internal urethral sphincter).These symptoms are clubbed together under the

term urethral syndrome. 25

Genital

• Atrophic vagina reduces the vaginal secretion, and dry vagina cause dyspareunia.

• Loss of libido adds to sexual dysfunction.

26

COMPLICATIONSor

LATE SEQUELAE

Menopause is a normal developmental process, but the decline in E can have

clinical sequelae.

27

– Vasomotor symptoms.• HTN

– Osteoporosis.

• Arthritis• Osteoporosis of vertebral bones, upper end of

hip joint,wrist• frature

– Cardiovascular disease.• ischaemic heart disease, MI, HTN• Stroke• Cardiac irregularities• Tachycardia

28

– Urogenital atrophy.• Prolape genital tract• Stress incontinence of urine & feces• Ano-colonic cancer

– Cognitive decline and Alzheimer's disease.

– Cataract, glaucoma, macular degeneration

– Skin changes and Tooth decay

29

• An incipient slowly progressing skeletal disorder:

microarchitectural detirioration of bone mass resulting in

increased fragility and predilection to frature in the absence of

sig. trauma30

Definition by WHO

OSTEOPENIA:• As a BMD b/w 1 and 2.5 SD below the young adult

mean peak

OSTEOPOROSIS:• As BMD which is 2.5 or more below the SD of mean

young adult values

31

Pathophysiology• Bone remodeling : at cellular level

osteoclastic and osteoblastic activity• Metabolic : osteocytes and lining

cells• Peak bone mass : by 35-40yrs• Then after slow subsequent age

related loss of bone mass: 0.4% annually for everyone

• Accelelarated rate in women: 2% cortical bone and 5% trabecular bone; estrogen def, Ca def, VitD def

32

• Bone Ca amts at 40 yo : 1200g; when drops to 750g: frature is liabile

• In elderly women : vertebral fraturegibbus formation, bent spine and shortening of height

• : hip frature

33

Other risk factorsFamily history of osteoporosis

Low Ca intake in diet

Smoking and excess of caffeine and alcohol intake

Early menopause

Low weight

Surgical menopause

Radiation menopause

Thyrotoxicity

Sedentery life syle

Women on GnRH, heparin, cortico steroids , danazol, clomiphene34

CARDIOVASCULAR DISEASE

• Estrogen is cardioprotective(antioxidant property also)

• After menopause HDL,LDL, total cholesterol ,

• Estrogen deficiencyatherosclerosis, ischemic heart disease, MI

• Risk factors: obese women with hypertension , previous thromboembolicepisodes 35

Stroke

• Incidence of stroke also increase in menopausal women

36

Skin changes• Collagen content is reduced, causing skin

to wrinkle

• The loss of collagen is more rapid in the first few years after menopause

• 30% of skin collagen is lost within the first 5 years.

• The rate is 2% per year for the first 10 years after menopause.

37

CNS

• ER are abundant in the brain. E have a role in many brain processes, and it’s absence result in physiologic and symptomatic changes.

• E is important for – cerebral blood flow– cerebral glucose administration– synaptic activity, neuronal growth– survival of cholinergic neurons– complex functions as cognition.

• The role of E deficiency in postmenopausal depression, declining cognitive function, dementia, and Alzheimer's disease is not clear.

38

Pyometra

• Years after menopause, women may develop senile pyometra cervical stenosis

• Rx : drainage by cervical dialatation under GA

39

Diagnosis1) History

menstrual abnormality

2) Symptoms:• vasomotor symptoms • vaginal dryness• urinary frequency• Insomnia• Irritability, anxiety• skin change• breast changes• urinary tract problem• pelvic floor change • skeletal change(backache, ).

40

3)Physical examination:

The clinical findings vary greatly depending on the time elapsed since menopause and the severity of the estrogen deficiency

Skin: thin ,dry Breast loss turgor The labia are small The uterus becomes much smaller The muscles of the pelvic floor are looser in

tone and are thin Prolapse may be present

41

4) Laboratory diagnosis

General examination: BP, Palpation of breasts, weight, hirsuitism Pap smear Mammography, pelvic US E2, FSH, LH determination Bone density study:

Dual energy X-ray absorptiometry(DEXA) Single or dual photon absorptiometry

42

Treatment

1)  Counselling

2) Mild tranquillizers

3)  Hormone replacement therapy(HRT)

43

Counselling The women often develops

pregnancy & cancer phobia.Duty of gynaecologist- exm.

&investigation.Pelvic ultrasound-ovarian size,

endometrial thickness, mammography & as well as E2 &FSH levels, when HRT is considered.

The advice on contraceptives is necessary. Until the menopause is well established & amenorrhea has lasted for 12 month, couple is advice to use barrier method.

Diet: least 1.2g of Ca, Vit A,C,E &400mg of Vit .D & Soya beans are good.

Weight bearing exercise delay onset of osteoporosis.

Mild tranquillizersAnti depressants like sulpirideReleives anxiety, depression,

sleeplessness

Hormone replacement therapy

Not all women require HRT

70-85% of women remain healthy need only good nutrition and healthy life style.

Indications of HRT1) Women having

climacteric symptoms

Vasomotor symptoms

Urinary symptoms

Sexual dysharmony

Established osteoporosis on x-ray /B.M.D. Measurements

2) All asymptomatic high-risk women havingPremature menopause (surgical / spontaneous)

Family history of osteoporosis

Thin, small sedentary women

Poor diet, excess alcoholCVD, Alzhemeir’s disease, colonic cancer

Corticosteroid & other medications

High urinary calcium / creatinine

Low plasma estradiol

Contraindications of HRTBreast cancer, uterine cancer or

family history of cancer.Previous history of

thromboembolic episode.Liver & gall bladder disease.

DRUGS USED IN HRTOestrogen ProgesteroneOther drugs:

◦Tibolone◦Raloxifene◦Soya◦Bisphosphonates

Estrogen therapyShort term estrogen therapy• 1) To releive symptoms like; hot flush, night

sweats, palpitations, disturbed sleep In smallest effective dose for 3-6 months Natural estrogens Oral premarin(Conjugated equine estrogen

(CEE): 0.625 mg daily) Ethinyl estradiol(0.01mg),Evalon(1-2mg),

micronized oestrogen are effective.

Medroxyprogestrone(10mg) or primolut-N (2.5mg) daily for 10-12d each month.

Combined hormone therapy(femet). 2mg 17-β-oestrodiol & 1mg of norethisterone acetate.

◦2) for dyspareunia, urethral syndrome and senile vaginitis Local estrogen cream(oestriol: 1/2g-

everyday-10-12 days each month for- 3-6 months)Short acting Cyclic progesterone administration is not

required.Postmenopausal withdrawal bleeding do

not occur.

Estring(vaginal ringreleases 5-10microgram - 3months)

Long term therapy:◦For delaying osteoporosis ◦Reduce the risk of CV disease◦Beyond 8-10yr

Oral Preparations of estrogenOral: -

◦ Conjugated equine estrogen (CEE): 0.625

mg daily

◦ Ethinyl estradiol : 0.01mg

◦ Micronised estrogen : 1-2g

ESTROGEN: ORAL

Advantages.

*Easy to take & cheap.*Good control due to short ½ life.

Disadvantages.*High dose required.*first pass effect in liver.

*daily intake

*tablet contain lactose& not suit to women who are allergic to lactose.

Transdermal Preparations of estrogen Transdermal (estradiol): -

◦ Patches: contains: 3-4mg; releases 50 micro gm / 24 hour

twice weekly.

◦ Gel :for improving collagen in skin 75 micro gm / 24 hours

daily.

ESTROGEN: TRANSDERMAL

Advantages.◦ Low dose, pure estradiol.◦ Avoids intestine & liver metabolism.◦ Reduces serum triglyceride & insulin resistance.◦ No thromboembolic risk or hypertension

Disadvantages.◦ More expensive◦ Not well tolerated in warm climates◦ Variable absorption.

ESTROGEN: IMPLANTS

Sub cutaneous implant (estradiol): -

◦ 25 / 50 / 100 mg. 6 monthly. Advantages.

◦ Pure estradiol, 6 monthly insertion, high level of estradiol in blood.◦ Avoids first pass effects◦ Better response in severe osteoporosis.

Disadvantages. ◦ Needs surgical procedure◦ Unable to control absorption◦ Difficult to remove pellet

THE RISKS OF HRTVaginal bleedingThromboembolismEndometrial cancer if E2 is taken

aloneBrest cancer due to progestogen

if HRT is taken over 5yrs.CHD in a women with CVD.

Progesterone Role in HRT

Prevents endometrial hyperplasia and cancer in non-hysterectomised women

Implant may replace oestrogen, where estrogen is c/I or sensitive

Prevents breast cancer Improves bone mineral density

◦ primolut-N 2.5mg ,◦medroxyprogestrone & duphaston◦Mirena IUCD- levonorgestrel

TiboloneSynthetic derivative of 19-nor-

testosterone.Weak oestrogenic, progestogenic, &

androgenic action.Endometrial hyperplasia Elevates the mood, relieves the VM

symptom, improves sex drive & reduces bone resoption.

Cardioprotection(red. TG) SE: wt gain, oedema, tenderness in

breast, GI symptom& vaginal bleed.

raloxifeneNon steroidal comp., SERM, reduses

the risk of fracture by 50%, esp. vertebra by BMD by 2-3%.

It causes 10% reduction in total cholesterol & LDL & HDL level.

It does not raise the level of triglycerides.so cardio protective for long term.

Reduces osteoporosis.

raloxifeneSide effects *hot flushes, cramps, venous

thrombosis, retinopathy.• Cotraindications *venous thrombosis *should be given with oestrogen *hepatic dysfunction *stop the drug 72 hr before surgery

*indomethacin,naproxen,ibuprofen,diazepam.

soyaIsoflavone.Abt 11g soya- 2-4mg

phytoestrogen-oetrogenic- non steroid plant product.

45-60mg soya daily –protective- breast cancer, liver disease &other side effect.

cholesterol ,LDL,TG & marginal HDL.

Antiviral, antifungal & anticarcinogenic.

Bisphosphonatesetidronate, tiludronate reduce bone

resorption through the inhibition of osteoclastic activity.

Elidronate(10mg/Kg f body wt-2W followed by a gap of 2-3M & this course is repeated for 10 such cycles.

Not given with Ca.(absorption )Overdose- hypocalcemia.Milk &antacid - gastric irritation.

alendronate (5mg daily or 35mg weakly) overdose-hypocalcemia.

Risedronate (5mg/D or35mg/M)- gastric side effect.

Zolendronic acid(once yr i.v 5mg over 15min) SE: osteonecrosis of the jaw & visual dis.

Calcitonin-inh. Osteoclast activity *nasal spray(single dose of 200IU

daily for 3M)

*NS can cause flushes, rhinitis, allergic reaction &nasal bleeding.

* fracture by 30%Subcutaneous inj. Of Calcitonin-GI

symptoms ,aneamia &inflammation of joint cause poor compliants so also the high cost.

Teriparatide-rec. formation of PIH *abt 20μg once daily SC inj. Ver.

Fracture-65% others-50% ,if used <2yr

*nausea, headache are the complication.

Strontium ranelate(1-2g daily orally) BMD-50%, very expensive, not

easily available.Clonidine- imidazole der. *treat hot flushes *effective in HT *dose 0.2-0.4mg daily.

PREMATURE MENOPAUSEDef: ovarian failure occurring 2 SD in

year before the mean menopausal age in the population.

Clinically: sec. amenorrhea for at least 3 months with raised FSH/LH & low E2 level in a women under 40 year of age.

Inc. 1% -be. 30yr-1:1000

-at 35yr-1:250 -be.40yr-1%

AETIOLOGY1.Genetic disorderchr. abnormalities (10-20%) –X sex chr. AD sex linked inheritance. Ovarian dysgenesis-30%2.Autoimmune disease(30-60%)Mumps, thyroid dys.,hypo parathyroidism,

& Addison’s dis.Ovarian biopsy –infiltration of follicle with

plasma cells& lymphocytes. CD8 & CD4 autoimmune d.Antiovarian Ab are present.

3.Tuberculosis4.Smoking5.Radiaton & chemotherapyReversibleRadiation up to 400 to 500 rads. restores

normal ovarian fun. in 50% cases.Alkalytic agents.6.HystrectomyKinking & blockage of ovarian vessels Tubectomy

7.Prolonged GnRH therapy.8.enz.defect-17α-hydroxylase &

galactosemia have adverse effect on oocytes – pri. Amenorrhea.

9.Resistant ovaryTerminology is used less frequently

these days.Follicles fail to respond to gonadotropin

stimulation.10.Induction of multiple ovulation in

infertility.

PATHOPHYSIOLOGYLack of receptors is explained as

the cause of non response of follicle.

C/FHot flushesSweatingInsomniaHeadachePsychologicalCancer phobiaPseudocyesisIrritabilityDepressionLack of conc.

INVESTIGATIONFSH level: 40mIU/ml or more.E2 level: 20pg/ml or lessThyroid fun., Ca level, chr. study,& thyroid

Ab.Blood sugar.X-ray pituitary fossa for the tumour.BMD study is not always necessary, it is

an invasive procedure. Ovarian biopsy.Ultrasound.Prolactin level.

COMPLICATIONSThe risks of osteoporosis &

cardiovascular diseases increase in premature menopause.

MANAGEMENT

1.Cause of premature menopause should be ascertained & the cause treated.

2.Ovulation induction or oocyte donation in IVF programme has caused pregnancies to occur in some cases.

3.Progestogen challenge test will indicate if menstruation can be induced, provided endometrium is primed with oestrogen.

4.Corticosteroid therapy is effective in autoimmune disease if Ab to sex hormone are present in the blood. Plasmapheresis has also been attempted.

5.A women with hypo-oestrogenism may require HRT or other drugs to prevent osteoporosis . oestrogen implant with progestogen or Mirena IUCD offers long-term HRT.

LATE MENOPAUSEDef: cond. in which menstruation

cond. beyond 52 year. Late menopause occurs in

women with fibroids and is seen in women who develop endometrial cancer. Often it is constitutional. Beyond 52 yr , endometrial biopsy is required to rule out endometrial pathology.

POSTMENOPAUSAL BLEEDING

Normally-1 yr POA –after 40 yr. however, VB –anytime after 6 MOA

in menopausal age postmenopausal bleeding & investigated.

without amenorrhea / irre. Bleeding , if the women over the age of 52 yr cont. to menstruate, she needs investigation to rule out endometrial hyperplasia & mali. Of genital tract.

AETIOLOGY

1.vulva-trauma , vulvitis ,benign & malignant lesions.

2.vagina-foreign body such as ring pessary for prolapse, senile vaginitis , vaginal tumour (benign as well as malignant) postradition vaginitis.

3.cervix-cervical erosion, cervicitis, polyp, decubitus ulcer in prolapse &cervical malignancy.

4.uterus-senile endometritis, tubercular endometritis, endometrial hyperplasia(10%) , polyp, endometrial carcinoma& sarcoma , & mixed mesodermal tumour.

5.Dysfunctional uterine bleeding, metropathia haemorrhagica, uterine polypi & endometrial hyperplasia.

6.Fallopian tube malignancy .

7. ovary- benign ovarian tumour such as benner tumour, granulosa & theca cell tumour, & malignant ovarian tumour.

8. Hypertension & blood dyscrasia.9. Urinary tract- urethral caruncle,

papilloma &CA of bladder. May be mistaken for genital tract bleeding.

10.bowel- bleeding from haemorrhoid , anal fissures, & rectal cancer may be misleading.

11.imp. Reason –indiscriminate. Prolonged use of oestrogen unopposed by progestogens, & HRT when applied clinically. Tamoxifen causes endometrial hyperplasia & cancer.

30-50% -PMB –malignancy of genital tract

-most common –endometrial cancer , cervical cancer& ovarian tumour.

Common benign conditions are endometrial hyperplasia and polypi.

C/FHISTORY *age –menarche & menopause *taking oestrogen & tamoxifen *prolapse details *abdominal pain &foul smelling

discharge- malignant tumours *urinary& rectal symptoms .

EXAMINATION *BP *GE- obesity& diabetes *abdominal pain *speculum & bimanual

examination

INVESTIGATIONAim: Excluding malignancy 1.Blood count & smear- blood dyscrasia.2.Blood sugar level.3.Cervical cytology-cervical lesion.4.Endometrial study.5.Sonosalpingography –endometrial

polyp.6.ultrasound- endometrial thickness

>4mm indicates the need of endometrial biopsy.

Several methodsDilatation & curettage (D&C) –

fractional curettage comprising separate scrap of endometrium &endocervix not only allows the exact site of malignancy if present, but also detect the extent of the tumour & staging.

Uterine cavity aspiration & endometrial sampling.

Vibra aspirator, Gravlee’s jet washer , Isaac’s aspirator & Pipelle aspiration –end. Sample.

7.Hystroscopy inspection& selective biopsy.

8.CT & MRI .9.Diagnostic laparoscopy .10.Cytoscopy & proctoscopy.

MANAGEMENT1. Treat the cause.2. When no cause is found, & if there has

been only one bout of bleeding, the pt should be kept under observation.

Abt 80% of cases do not bleed again. If cond. to bleed- laparotomy. An undiagnosed small tumour may be

discovered & dealt appropriately. – AH with bilateral oophorectomy histopathological study.

9292

Thank you