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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