MenopauseMenopause

Sayed Muhammad Hussaini Sayed Muhammad Hussaini Batch KBatch K08-19208-192

1-Introduction1-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.

- - Climacteric:Climacteric: which is by dictionary definition is period which is by dictionary definition is period of life when fertility and sexual activity decline. It occurs of life when fertility and sexual activity decline. It occurs due to the dwindling function of ovaries which is due to the dwindling function of ovaries which is manifested by physical and psychological changes in manifested by physical and psychological changes in the body. It is a wide term leading to:the body. It is a wide term leading to:

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

Definitions: Definitions:

- - Perimenopause:Perimenopause: 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 menopausal episodes of ammenorrhea and intermittent menopausal symptoms.symptoms.

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

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

- - Smokers experience menopause up to 2 years earlier.Smokers experience menopause up to 2 years earlier. - Mean age – 51 years.- Mean age – 51 years.

Definitions:Definitions:

Premature menopause:Premature menopause:

It occurs b/w ages 30 and 40 years and is mostly It occurs b/w ages 30 and 40 years and is mostly idiopathic, but can also occur after radiation therapy and idiopathic, but can also occur after radiation therapy and oophorectomy.oophorectomy.

- Premature ovarian Failure:Premature ovarian Failure:- It occurs before age 30 years and may be associated with It occurs before age 30 years and may be associated with

autoimmune disease or Y chromosome mosaicism.autoimmune disease or Y chromosome mosaicism.

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The Reproductive CycleThe Reproductive Cycle

Hormonal changesHormonal changes

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FSH

Ovary

Hypothalmus

Inhibin B+

GnRH

Normal Ovary

Hormonal changesHormonal changes

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FSH

Ovary

Hypothalamus

Estradiol / Inhibin B+

GnRH

Aging Ovary

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FSH

Ovary

Hypothalmus

Estradiol / Inhibin B+

GnRH

Menopausal Ovary

Hormonal changesHormonal changes.

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

dramatic just before menopause.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 estrogen level → lead todecrease progesterone but not estrogen level → lead to DUB and endometrial HyperplasiaDUB and endometrial Hyperplasia - at menopause dramatic decrease of estrogen→menstruation - at menopause dramatic decrease of estrogen→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 due to increase LH action on stromal cells. But, main testosterone due to increase LH action on stromal cells. But, main postmenopausal estrogen is estrone produced by Peripheral fat.postmenopausal estrogen is estrone produced by Peripheral fat.

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. Cardiovascular Symptoms2. Cardiovascular Symptoms - Hypertension: has no direct relation with menopause, just - Hypertension: has no direct relation with menopause, just

a coincidence. a coincidence. - Palpitation- Palpitation - Heart disease: the incidence of coronary thrombosis - Heart disease: the incidence of coronary thrombosis

increases rapidly after menopause.increases rapidly after menopause.

Symptoms……Symptoms……

3. Psychological/Neurological symptoms:3. Psychological/Neurological symptoms:

Anxiety, depression, loss of libido, Alzheimer, insomnia.Anxiety, depression, loss of libido, Alzheimer, insomnia.

4. General Symptoms:4. General Symptoms:

fatigue, weakness, headache, vertigo, breast tendernessfatigue, weakness, headache, vertigo, breast tenderness

skin pigmentation. She may complain of dyspareunia.skin pigmentation. She may complain of dyspareunia.

Gastrointestinal symptoms in the form of increase or Gastrointestinal symptoms in the form of increase or decrease appetite. decrease appetite.

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Vasomotor SymptomsVasomotor Symptoms Most often begin in perimenopauseMost often begin in perimenopause Sudden onset reddening of the skin Sudden onset reddening of the skin

(head/neck/chest), feeling of intense (head/neck/chest), feeling of intense body heat, profuse perspirationbody heat, profuse perspiration Speroff Speroff

Intervals vary (minutes to hours)Intervals vary (minutes to hours) More frequent and severe at nightMore frequent and severe at night Generally stop spontaneouslyGenerally stop spontaneously

w/in few years, may persist w/in few years, may persist for many yearsfor many years

– 12-15 % of women in 60’s12-15 % of women in 60’s– 9% of women after age 70 9% of women after age 70 CasperCasper

After menopauseAfter menopause

Atrophic changes:Atrophic changes: Vagina Vagina *vaginitis due to thinning of epithelium, ↓ PH and lubrication.*vaginitis due to thinning of epithelium, ↓ PH and lubrication. *dyspareunia→due to decrease vascularity and dryness*dyspareunia→due to decrease vascularity and dryness Decrease size of cervix and mucus with retract of Decrease size of cervix and mucus with retract of

segumocolumnar (SC) junction into the endocervical canal.segumocolumnar (SC) junction into the endocervical canal. Decrease size of the uterus, shrinking of myoma & Decrease size of the uterus, shrinking of myoma &

adenomyosis.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

After menopauseAfter menopause

Decrease size of breast and benign cysts.Decrease size of breast and benign cysts.

Skin Collagen – Skin Collagen – ↓ collagen & ↓ collagen & thickness thickness →→ ↓↓ elasticity of the skin.elasticity of the skin.

IV. Late effect of MenopauseIV. Late effect of Menopause

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

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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

Risk factorsRisk factors

..Age Race Oestrogen Wt Diseases

Diet Drugs Lifestyle

Low Ca.

Low Vit D

Alcohol

Smoking

SedentaryOsteoporosis

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Pathogenesis of Estrogen Pathogenesis of Estrogen Deficiency and Bone LossDeficiency and Bone Loss

Estrogen loss triggers increases Estrogen loss triggers increases in IL-1, IL-6, and TNF.in IL-1, IL-6, and TNF.

Increased cytokines lead to increased Increased cytokines lead to increased osteoclast development and lifespan.osteoclast development and lifespan.

Increased turnover of osteoblasts.Increased turnover of osteoblasts. Impacts vitamin D metabolismImpacts vitamin D metabolism Impacts on renal and intestinal handling Impacts on renal and intestinal handling

of calciumof calcium

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Consequences of OsteoporosisConsequences of Osteoporosis

Spinal (vertebral) compression fractures– Back pain– Loss of height and

mobility– Postural deformities

Colles’ (forearm) fractures

Hip Fractures Tooth loss

Diagnosis – (DEXA-Dual Energy X-ray Absorptometry)Diagnosis – (DEXA-Dual Energy X-ray Absorptometry)-for Assessment of bone densmetry to demonstrate if bone -for Assessment of bone densmetry to demonstrate if bone density above or below fracture threshold.density 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 moderator [SERMs] that bind with a high affinity to estrogen

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

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

Treatment:Treatment:

Non Hormonal:Non Hormonal: 1. Calcium 1200-1500 mg per day1. Calcium 1200-1500 mg per day

2. Calcium and Vit. D every day2. Calcium and Vit. D every day 3. Calcitrol/Calcitonin3. Calcitrol/Calcitonin 4. Raloxifene4. Raloxifene 5. Biphosphonates5. Biphosphonates 6. Exercise6. Exercise 7. Phytoestrogens7. Phytoestrogens For severe hot flushes vit. E, antidepressants or For severe hot flushes vit. E, antidepressants or

gabapentin may be prescribed.gabapentin may be prescribed.

Hormonal treatmentHormonal treatment

When hormones are prescribed for When hormones are prescribed for climacteric symptoms it is called climacteric symptoms it is called hormones replacement therapy.hormones replacement therapy.

HRT HRT has benefits for the patients but has benefits for the patients but there are some disadvantages as well.there are some disadvantages as well.

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Hormone Replacement TherapyHormone Replacement Therapy

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

Decrease hot flashesDecrease hot flashes Prevents/treats osteoporosis and hip and Prevents/treats osteoporosis and hip and

vertebral fracturesvertebral fractures Prevents/treats urogenital atrophyPrevents/treats urogenital atrophy

Benefits

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Hormone Replacement TherapyHormone Replacement Therapy

Increased risk for venous thrombosis Increased risk for venous thrombosis and embolism**and embolism**

Increased risk for breast cancer with Increased risk for breast cancer with prolonged (>3-5yrs) use (EPT, not ET) prolonged (>3-5yrs) use (EPT, not ET)

Increased risk for endometrial cancer Increased risk for endometrial cancer with ET (not EPT) (if uterus present)with ET (not EPT) (if uterus present)

****may be dependent on route of administrationmay be dependent on route of administration

Risks

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

Hormones of HRTHormones of HRT

Following hormones may be used to control the symptoms.Following hormones may be used to control the symptoms. 1. Estrogens only1. Estrogens only 2. Estrogens and Progestogens2. Estrogens and Progestogens a. Continuous (No bleeding takes place)a. Continuous (No bleeding takes place) b. Cyclical (bleeding takes place)b. Cyclical (bleeding takes place) 3. Estrogens and Androgens3. Estrogens and Androgens 4. SERM (Selective estrogen receptor modulators)4. SERM (Selective estrogen receptor modulators) 5. Tibolone5. Tibolone 6. Testosterone 6. Testosterone

1.Estrogens1.Estrogens

Treatment of choice for patients who had hysterectomy.Treatment of choice for patients who had hysterectomy. With administration of estrogens the symptoms are With administration of estrogens the symptoms are

improved which are due to reduced production of estrogens improved which are due to reduced production of estrogens by the ovary.by the ovary.

PREPRATIONS:PREPRATIONS: a. Conjugated equine estrogens (premarine) is most a. Conjugated equine estrogens (premarine) is most

commonly prescribed for those patients who had commonly prescribed for those patients who had hysterectomy. Tablets:0.3-1.25 mg daily. hysterectomy. Tablets:0.3-1.25 mg daily.

b. Less commonly prescribed due to metabolic side effects b. Less commonly prescribed due to metabolic side effects is ethinyl estradiol. Tablets 0.01-0.05 mg daily. is ethinyl estradiol. Tablets 0.01-0.05 mg daily.

Routes of administration of estrogens are oral, transdermal, Routes of administration of estrogens are oral, transdermal, patches, gel, and subcutaneous insertion. patches, gel, and subcutaneous insertion.

2. Estrogens and Progestogens2. Estrogens and Progestogens

They are prescribed for those patients who have intact uterus.They are prescribed for those patients who have intact uterus. PREPARATIONS:PREPARATIONS: a. Sequential combined (femoston) a. Sequential combined (femoston) Tablets are taken every day for 21 days and stopped for 7 days. They Tablets are taken every day for 21 days and stopped for 7 days. They

contain estradiol 1-2 mg plus dihydroprogesterone 10 mg. But women contain estradiol 1-2 mg plus dihydroprogesterone 10 mg. But women get withdrawal bleeding every month.get withdrawal bleeding every month.

b. Continuous combined Pill:b. Continuous combined Pill: Tablets are taken continuously without a break.Tablets are taken continuously without a break. Include climen plus estradiol plus norethisterone.Include climen plus estradiol plus norethisterone. There is no withdrawal bleeding.There is no withdrawal bleeding.

3. Estrogens and androgens3. Estrogens and androgens

In postmenopausal women there is reduced level of In postmenopausal women there is reduced level of androstenedione.androstenedione.

Preparations containing methyl testosterone and ethinyl Preparations containing methyl testosterone and ethinyl estradiol are available in the market.estradiol are available in the market.

Tablets of Mixogen contain both these hormonesTablets of Mixogen contain both these hormones They are good for libido, the injection is effective for 3 to 6 They are good for libido, the injection is effective for 3 to 6

months.months.

4.SERM4.SERM

This specifically act on bones,help to stop This specifically act on bones,help to stop osteoporosis. They do not cause withdrawl osteoporosis. They do not cause withdrawl bleeding.bleeding.

1.Tamoxifen(Nolvadex) has bone and 1.Tamoxifen(Nolvadex) has bone and endometrium agonist effect but antagonist endometrium agonist effect but antagonist effects on breasts.effects on breasts.

2.Raloxifene(Evista) has bone aggonist 2.Raloxifene(Evista) has bone aggonist effects but endometrial antagonist effects.effects but endometrial antagonist effects.

Tibolone and testosterone Tibolone and testosterone

Tibolone tablet is taken every day. There is Tibolone tablet is taken every day. There is no withdrawal bleeding. no withdrawal bleeding.

Testosterone implants is given by deep Testosterone implants is given by deep intramuscular route every 4 to 6 months. intramuscular route every 4 to 6 months. injections 50 to 100 mg .injections 50 to 100 mg .

Recommendations for HRTRecommendations for HRT

The The only indicationonly indication for HT is vasomotor symptoms. It should not for HT is vasomotor symptoms. It should not be used for prevention of cardiovascular diseases. Although HT is be used for prevention of cardiovascular diseases. Although HT is effective for prevention of post menopausal osteoporosis consider non effective for prevention of post menopausal osteoporosis consider non estrogen medication first if osteoporosis prevention is the sole reason estrogen medication first if osteoporosis prevention is the sole reason for using HT.for using HT.

The The lowest doselowest dose of HT that will treat the symptoms should be of HT that will treat the symptoms should be used.used.

The The shortest durationshortest duration of HT that will treat symptoms should of HT that will treat symptoms should be used.be used.

Optimally do not exceed 4 yearsOptimally do not exceed 4 years. The increase in . The increase in breast cancer risk with HT was not found prior to 4 years.breast cancer risk with HT was not found prior to 4 years.