NORDSTROMMenopause Talk

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    MENOPAUSE: What everymedical student should know

    Sherry K Nordstrom, MD

    Asst Prof of OB/GYN, UIC College of

    Medicine

    Learning Objectives

    Understand pathophysiology of normal and

     premature menopause

    • Know major symptoms of menopause

    • Learn about various treatment options formenopausal symptoms

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    Definitions

    • Menopause - the cessation of menses for at

    least one year due to loss of ovarian activity

    • Perimenopause - the time surrounding

    menopause when symptoms usually occur 

    • Postmenopause - the lifespan of a woman

    after cessation of menses

    Characteristics

    • Average age at menopause is 51

    range 48-55

    • Average age at perimenopause (based on

    irregular menses) is 47.6mean duration of 4 years

    • Average duration of postmenopause is

    >30 years

    • Smokers have menopause 2-3 years earlier

    than nonsmokers

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    Pathophysiology of Ovulation

    • FSH (Follicle Stimulating Hormone) tells

    the ovary to recruit eggs

    • Estrogen is made by the developing eggs

    • LH (Luteinizing hormone) peaks at

    midcycle (with estrogen and FSH) resulting

    in ovulation

    • Post-ovulation, the corpus luteum makes progesterone until lack of pregnancy results

    in lowered progesterone and menses

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    Pathophysiology of

     perimenopause

    • Anovulation more common in 40s as

    ovaries less responsive to FSH

    • FSH levels increase to try to bribe ovaries

    into responding

    • Estrogen levels decrease as fewer follicles

    are recruited

    • Progesterone levels fluctuate as corpusluteum produces varying amounts

    Pathophysiology of Menopause

    • Fewer and fewer follicles are recruited until

    no follicles develop at all

    • FSH and LH levels become persistantly

    elevated• Estrodiol levels stabilize at 10-20 pg/ml

    • Testosterone levels stable, but ovarian

     production increases - androstenedione

    decreases by half so have relative androgen

    deficiency

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    Task 

    • Break into small groups

    • List 5 symptoms of

    menopause/perimenopause besides hot

    flashes• List one treatment for each symptom

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    Irregular Cycles

    • 90% of women have irreg cycles prior to

    cessation of menses

    • Cycle length shortens, as short as 21 days,

    followed by skipped periods

    • Occasionally see longer cycle length

    • Flow may be lighter or heavier 

    When to Worry

    • If bleeding closer than every 21 days

    • If bleeding lasts longer than 10 days

    • If bleeding heavy enough to soak a maxipad

    in 1 hour or less for several hours in a row

    • If any of the above, the patient needs further

    evaluation

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    What to do:

    • EMB (endometrial biopsy)

    • D&C (rare now)

    • Ultrasound evaluation of uterus with

     possible saline infused sonohysterogram

    (SIS)

    • Hormonal treatments such as progesterone,

    GnRH agonists or OCPs• Surgical treatments such as endometrial

    ablation or hysterectomy

    Hot Flashes

    • Also called hot flushes or vasomotor events

    • Sudden onset of feeling of intense heat with

    reddening of face/chest/head skin followed

     by profuse perspiration• Lasts a few seconds - several minutes

    • Present in 85% of women, last >5 years

     postmenopause in 25-50%

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    Hot Flashes

    • Frequency is variable - from one per week

    to several per hour - changes as womangoes through menopause

    • Cause sleep disturbances - may be the

    etiology of emotional lability in menopause

    • Triggered by stress

    • Embarrassing - happens when women at peak of careers, causes feeling of loss of

    control

    Hot Flashes - Etiology

    • Primarily related to estrogen deficiency but

    not the whole answer 

    • Estrogen replacement reduces flash

    frequency and severity, but may noteliminate them

    • Seen in women on OCPs, some medical or

     psychiatric conditions

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    Hot Flashes - Treatment

    • Estrogen replacement - most effective

    • Wear layered clothing, keep cool

    • Progesterone replacement - effective alone,

    can be used orally or transdermally

    • Botanical remedies - black cohosh, red

    clover, soy products with phytoestrogens

     being studied - minimal success• Clonidine, SSRI’s, Gabapentin with some

    success

    Vaginal Dryness

    • Woman often describes dryness or irritation

    • Due to atrophy of mucosal surfaces

    • Causes vaginitis, pruritus, dyspareunia,

    stenosis of vaginal opening andincontinence

    • Symptoms vary with sexual activity, size of

    vaginal opening prior to menopause, patient

    tolerance. Many patients with atrophic

    appearing vaginas are asymptomatic

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    Vaginal Dryness - Treatment

    • Lubrication - KY jelly, Astroglide, Vaginal

    moisturizers (Replens)

    • Estrogen replacement - topical or oral

    • Encourage maintenance of sexual activity -

    can improve blood flow to area and

    maintain vaginal caliber, reducing

    symptoms

    Emotional Lability

    • Extremely variable symptom - depression

    most common, also see mania

    • Possibly related to sleep disturbances

    • Psychiatry literature feels symptomscombination of hormonal changes and life

    stressors often occuring at the same time

    (children leaving home, aging parents, etc)

    • Estrogen replacement may help

    • Treat in conjunction with psychologist

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    Medical Risks Related to

    Menopause

    • Osteoporosis risk increases - lose 2% of

     bone/year 

    • Cardiovascular disease risk doubles

    • Alzheimer’s Disease - 70% of women

    without HRT have AD by age 90

    Women have 2-3x risk of men

    Diagnosis of Perimenopause

    • Clinical symptoms in appropriate age group

    • Lab tests not necessary in all women, but

    can help in unsure cases

    • FSH, LH, estrogen levels. Remember allthese fluctuate in perimenopause so all may

     be normal but pt still perimenopausal.

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    Diagnosis of Menopause

    •  No menses for > 12 months in appropriate

    age group

    • Always see elevated FSH (>25) but don’t

    always need to test if obvious.

    • Premature menopause - women < 40 years,

    occurs in 1% of population. Must have

    elevated FSH to diagnose.

    Treatment of Menopause

    •  No medical “treatment” is required for most

    women

    •  Need to understand pts views on symptom

    control and preventative medicine• Good opportunity for education regarding

    healthy lifestyles, weight loss, exercise

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    Supportive Care

    • Educate - Woman needs to know which

    symptoms are normal, which are cause forconcern

    • Address individual symptoms such as hot

    flashes or vag dryness

    • Offer health screening - pap, mammo, chol,

    TSH, colonscopy, etc.• Provide education about diet, exercise,

    smoking cessation

    Complementary Medicines

    • Many (approx 70%) use alternative

    treatments for menopausal symptoms - ask 

    • Patients may worry HRT not “natural”

    • Lots of research ongoing in this area• Herbal supplements not regulated by FDA

    so dose, strength not reliable. Risks not

    well studied

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    Types of Complementary

    Medications

    • Soy - contains phytoestrogens, may provide

    hot flash and vaginal atrophy relief 

    • Black Cohosh - hot flashes – 

    • Red clover - hot flashes

    • Gingko baloba - memory loss/mood swings

    • Wild yam creams - progesterone but not

     bioavailable for humans so useless

    • St John’s wort - depression/mood swings

    Hormone Replacement Therapy

    • Replacement of estrogen to physiologic

     premenopausal levels

    • Women with hysterectomies need only

    estrogen• Women with uteri need progesterone as

    well to decrease risk of endometrial

    hyperplasia and carcinoma present with

    unopposed estrogen use

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    Estrogen

    • Many forms available

    • Synthetic and “natural” sources

    • #1 selling estrogen is Premarin (Pregnant

    MARe urINe) which is conjugated

    estrogens at .625mg - best studied form

    • Can be taken orally, vaginally,

    intramuscularly or transdermally

    Estrogen

    • Monitor effectiveness based on pt

    symptoms and side effects

    • Can use timed blood or salivary estrogen

    levels to help monitor • FSH levels not helpful

    • Use lowest dose that provides relief - .3mg

    Premarin still offers osteoporosis protection

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    Estrogen Side Effects

    • Irregular vaginal bleeding

    • Breast tenderness

    •  Nausea

    • Headaches including migraines

    • Weight gain

    • Most resolve or reduce with continued use

    • Often cause discontinuation - must warn

     patients

    Progestins

    • Reduces risk of endometrial cancer back to

     baseline in estrogen users

    • Can reduce hot flashes, osteoporosis on own

    • Synthetic and natural types available -synthetics have many side effects

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    Progestins - side effects

    • Synthetics:

    Weight gain, breast tenderness,depression, irritability, bloating, headaches

    • Generally more severe than estrogen side

    effects

    •  Naturals:

    Drowsiness, breast tenderness, bloating• Usually milder than synthetics

    HRT regimens

    • If hysterectomy - estrogen alone

    Common doses Premarin .625mg or

    0.3mg daily, Estrace 1mg or 2mg daily

    • If have uterus - use combined HRT(estrogen and progestin)

    2 types are sequential or continuous

    combined

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    Sequential HRT

    • Use estrogen daily and use progestin for

     part of month

    • Most common Premarin .625mg qd with

    Medroxyprogesterone (Provera) 10mg or

    5mg for 10-14 days of the month

    • 80-90% will get a withdrawal bleed

    monthly• Progestin side effects generally worse with

    intermittent use and relatively high dose

    Continuous Combined HRT

    • Estrogen and progestin daily

    • Most common Premarin .625mg with

    Provera 2.5mg daily

    • 40-60% have breakthrough bleeding in first6 months, 20% lasts > 1 year 

    • Generally lower side effects related to lower

     progestin dose

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    Continuous Combined HRT

    • Amenorrhea desirable for women

    • If not achieving, can change progestin type

    or dose

    • Amenorrhea more common if pt further

    from natural cessation of menses

    Benefits of HRT

    • Reduces hot flashes, vaginal dryness,

    osteoporosis (fracture risk), and colon

    cancer risk (WHI study)

    • May improve short term memory issues,may improve emotional lability

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    Risks of HRT

    • Combined HRT increases risk of breast

    cancer, heart attack, stroke, DVT (WHIstudy)

    • Estrogen alone increases DVT, slight

    increase in stroke

    • If uterus present and take estrogen alone,

    increases risk of endometrial cancer (1-2%),7% develop hyperplasia

    • Lowers seizure threshold in some patients

    Breast Cancer Risk 

    1/9 women who live to 85 develop breast

    cancer 

    • RR with combined HRT 1.25-1.33 (WHI

    and others)• RR with estrogen alone 0.8 (WHI)

    • Increases with prolonged use of combined

    HRT

    • Counterintuitively, mortality among HRT

    users with breast cancer is less RR 0.82

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    Breast Cancer Risk 

    •  Need to discuss with patient

    • Women with strong family histories should

     probably avoid HRT

    • Look at overall risks for each patient - heart

    disease, osteoporosis, colon cancer,

    Alzheimer’s Disease as well as pts

    individual symptoms related to menopause

    Women with Breast Cancer 

    • Some have very symptomatic menopause

    • Some choose to use HRT, many try herbal

    remedies - data not great to say herbal

    remedies safer, but phytoestrogens appearlower risk

    • Remember cancers can have Estrogen and

    Progesterone receptors

    • Requires extensive discussion between the

     patient, her gynecologist and her oncologist

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    Why use HRT in the post-WHI

    era?

    • Reduces menopausal symptoms better than

    any other treatment available

    • Prevents some future diseases - osteoporosis

    and colon cancer 

    • May prevent other diseases - Alzheimer’s

    Disease

    Why do many patients and

    doctors avoid HRT?

    • Increased risk breast cancer, DVTs, heart

    attacks and strokes (Combined HRT).

    • Side effects - wt gain, bloating, breast

    tnederness, irregular bleeding, etc• Doesn’t completely eliminate menopausal

    symptoms

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    Individualize Therapy

    • Each patient and physician has to weigh the

    risks and benefits for the individual beforeundertaking HRT

    • Have frequent f/u visits after initiating HRT

    to assess side effects and concerns

    • Reevaluate decision to continue or not on an

    annual basis

    Remember 

    • Menopause will happen to every woman if

    she lives long enough

    • Symptoms of menopause extremely

    variable in severity• Good opportunity for lifestyle

    education/modification and screening for

    diseases

    • May not require any treatment