MENOPAUSE: What every medical student should know

MENOPAUSE: What every
  medical 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 for
  menopausal symptoms

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 47.6
      mean duration of 4 years
• Average duration of postmenopause is
      >30 years
• Smokers have menopause 2-3 years earlier
  than nonsmokers

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

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 corpus
  luteum 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

Task
• Break into small groups
• List 5 symptoms of
  menopause/perimenopause besides hot
  flashes
• List one treatment for each symptom

Clinical Presentation
 •   Irregular cycles
 •   Hot flashes
 •   Vaginal dryness or irritation
 •   Emotional lability
 •   Memory lapses
 •   Decreased libido
 •   Facial hair/acne
 •   Palpitations

10 WAYS TO KNOW IF YOU HAVE
"ESTROGEN                   ISSUES"
1. Everyone around you has an attitude problem.
2. You're adding chocolate chips to your cheese omelet.
3.The dryer has shrunk every last pair of your jeans.
4. Your husband is suddenly agreeing to everything you say.
5. You're using your cellular phone to dial up every bumper sticker
that says "How's my driving-call 1-800-***!
6
. Everyone's head looks like an invitation to batting practice.
7. You're convinced there's a God and he's male.
8. You can't believe they don't make a tampon bigger than Super Plus.
9. You're sure that everyone is scheming to drive you crazy.

10. The ibuprofen bottle is empty and you bought it yesterday.

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

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%

Hot Flashes
• Frequency is variable - from one per week
  to several per hour - changes as woman
  goes 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 not
  eliminate them
• Seen in women on OCPs, some medical or
  psychiatric conditions

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 and
  incontinence
• Symptoms vary with sexual activity, size of
  vaginal opening prior to menopause, patient
  tolerance. Many patients with atrophic
  appearing vaginas are asymptomatic

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 symptoms
  combination 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

Memory Lapses
• Well documented decrease in short term
  memory and concentration
• Generally transient, improves after
  completion of menopause
• May not return to premenopausal baseline
• Some data suggest estrogen helps return
  memory to baseline and may offer
  protection from Alzheimer’s Disease later
  in life - jury still out.

           Decreased libido
• Makes evolutionary sense
• Problematic for relationships
• Almost always multifactorial
• Can measure testosterone levels and replace
  testosterone
• Estrogen also can help

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 all
  these fluctuate in perimenopause so all may
  be normal but pt still perimenopausal.

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

Supportive Care
• Educate - Woman needs to know which
  symptoms are normal, which are cause for
  concern
• 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

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

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

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

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

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 first
  6 months, 20% lasts > 1 year
• Generally lower side effects related to lower
  progestin dose

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

Risks of HRT
• Combined HRT increases risk of breast
  cancer, heart attack, stroke, DVT (WHI
  study)
• 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

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 appear
  lower risk
• Remember cancers can have Estrogen and
  Progesterone receptors
• Requires extensive discussion between the
  patient, her gynecologist and her oncologist

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

Individualize Therapy
• Each patient and physician has to weigh the
  risks and benefits for the individual before
  undertaking 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