MENOPAUSE

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					     MENOPAUSE
40 million menopausal women in
        the U. S. presently
                       DEFINITION
 Spontaneous or Natural Menopause – 12 months of
  amenorrhea with no obvious pathological cause. Age
  range of onset is 40-58 years with the average age of
  51.4 years.
 Induced Menopause– due to surgery, chemotherapy or
  radiation therapy which can happen at any age.
 Premature Menopause or Ovarian Failure –defined as
  less than age 40.
       Transient – due to eating disorders or stress.
       Permanent – due to autoimmune disorders or genetic
        abnormalities (may be confirmed by karyotyping), usually 2/3 of
        the causes are idiopathic.
                   DIAGNOSIS
   A woman’s medical and menstrual hx and symptoms are
    sufficient to confirm the diagnosis of menopause.
   Serum FSH can potentially allow an earlier diagnosis of
    menopause but must be consistently elevated > 30
    mlU/ml.
   Hormonal contraceptives may lower FSH levels making
    it difficult to diagnose menopause – measuring FSH on
    the 7th pill free day was not a sensitive test. You may
    need to measure FSH:LH ratio looking for > than 1 or
    estradiol < than 20 pg/ml on the 7th pill free day.
   Always remember thyroid disease can mimic
    menopause, a TSH measurement may be necessary.
           Menopausal Symptoms
   Vasomotor Symptoms – Hot
    flashes and night sweats. In the
    U.S., about 75% of women
    experience vasomotor symptoms
    during the transition from
    perimenopause to
    postmenopause which last a
    median of 3.8 yrs. 25% of
    women have symptoms that
    continue for longer than 5 yrs.
    90% of women experience
    vasomotor symptoms with
    surgical menopause and their
    symptomatology may be worse
    than for women experiencing
    spontaneous menopause.
     Menopausal Symptoms
 Vulvar and Vaginal Atrophy with vaginal
 dryness and painful intercourse. Lack of
 estrogen also causes the urethra to
 become thinner and less efficient with
 detrusor pressure at the urethral opening
 decreasing, both during and after voiding.
 These changes increase a women’s risk of
 vaginal and urinary tract infections, and
 also urinary incontinence.
       Menopausal Symptoms
 Sexual Dysfunction - ? Related to all of the
  changes of the genitourinary tract can result in
  dyspareunia, leading to a decreased interest in
  sexual intercourse. Fatigue and depression
  brought on by the vasomotor symptoms and
  sleep disturbances of menopause can
  exacerbate this lack of interest in coitus.
 Also possible decrease levels of endogenous
  testosterone especially in women who have
  undergone sugical menopause may cause
  decreased libido.
   Do You Treat with Hormonal
          Therapy???
 The Women’s Health Initiative Study was
 terminated in 1998 due to harmful
 outcomes associated with hormonal
 replacement therapy such as an increase
 in invasive breast cancer, coronary heart
 disease, pulmonary embolism and stroke.
 Although it was the largest and best
 controlled, blinded study it had several
 shortcomings.
    Women’s Health Initiative Study
   Average age of women in the trail was 63.2. This mean does not
    reflect the customary hormonal therapy user who is 10 to 30 years
    younger.
   Only one regime of hormonal replacement, 0.625mg of estrogen
    with 2.5mg of progesterone was used.
   The women used in the study had an overall higher risk for heart
    disease than the general population.
   Breast Cancer was associated with those women who had been
    previous on hormonal replacement therapy suggesting that
    exposure to hormones required at least 5 years before an effect was
    noted and also those women diagnosed in the first year of the trial
    suggest that the cancer was preexisting. The increase risk is small
    in the WHI study, being 4 to 6 additional invasive cancers per
    10,000 women who use it for 5 or more years.
   The WHIMS, a supplementary study to the WHI, found an increase
    in Alzheimer. The findings of increase dementia was for those
    women over the age of 65. These findings have little relevance to
    hormonal replacement therapy given to women during the
    menopausal transition who are 10 to 15 years younger.
   The HERS study (mean age of
    66.7 years and established
    CHD) showed a increase in
    cardiovascular events in the first
    year and a decrease over time,
    suggesting that an at-risk group
    of women were affected
    particularly in the first year. The
    WHI study also observed an
    increase in heart attacks during
    the early stages of treatment.
    The two studies did reinforce
    that older women with CVD who
    have not taken hormonal
    replacement therapy should not
    begin treatment.
      So what about lower doses of
         hormonal therapy???
   The HOPE study examined the use of lower doses in
    healthy women age 40-65 and found that similar benefits
    were achieved regarding reduction in hot flashes, and
    prevention of bone loss. The Nurses Health Study has
    suggested that lower doses may protect against stroke,
    with the study demonstrating absolute risk of stroke
    almost tripled for women on at least 0.625mg of estrogen
    as compared with those taking a 0.3 mg dose. With
    respect to breast CA, studies, though controversial,
    contend that there is direct evidence to suggest that
    lover doses are correlated with a lower risk of breast
    cancer.
   Today the general indications for hormonal
    therapy are the treatment of moderate to severe
    menopausal related vasomotor symptoms and
    the prevention and possible treatment of
    osteoporosis. Women at high risk for serious
    medical outcomes with the use of estrogen
    include those with a history of breast cancer,
    those with an elevated risk for both ovarian and
    breast CA due to genetic factors, family hx or
    both; and those at high risk for CVD. Other risk
    factors include hx of PE, DVT, CVA or liver
    disease.
      Using Hormonal Preparations
   When the benefit outweighs
    the risk consider using
    hormonal therapy in lower
    doses for shorter periods of
    time.
   If lower doses not effective
    than consider standard dose
    therapy or twice daily
    therapy with half doses or
    even consider transdermal
    administration (bypasses the
    liver so no increase in TG or
    HDL.) which delivers more
    consistent blood levels of
    estrogen. Remember if the
    woman has a uterus, you
    must also treat with both
    estrogen & progesterone.
      Oral Estrogen Products
 Conjugated   Equine Estrogen – Premarin,
  doses are 1.25, 0.9,0.625, 0.45, 0.3mg/d
 Synthetic Conjugated Estrogen –
  Cenestin, 0.3, 0.45, 0.625, 0.9, 1.25
 Estradiol – Estrace, 0.5,1.0, 2.0 –
  transdermal patches are made of this.
 Very few head to head trials comparing
  different estrogens
        Estrogen/Progesterone
    Preparations for Postmenopausal
                   Use
   Continuous combined
                            Continuous combined
    has decrease rate of
    breakthrough             – Prempro
    bleeding and fewer      Continuous Cyclic –
    endometrial bx than      Premphase
    cyclic regimen.         Intermittent Combined
                             – Prefest
                            Transdermal
                             Continuous
                             Combined -
                             Combipatch
        Hormonal Treatments
 If perimenopausal
  and still having
  menses, consider low
  dose OCPs
 Progesterone alone
  can be used to tx
  vasomotor S/S but
  like estrogen has
  been linked to
  increase risk of breast
  cancer.
When Hormone Therapy isn't an
          Option
                  Effexor 37.5-75mg
                  Paxil 12.5-25mg/day
                  Prozac 20mg/day
                  Neurontin 300mg Qd-
                   TID
                  Clonidine 0.05-0.1mg
                   BID – consider
                   transdermal for
                   consistant blood
                   levels
                  SSRI’s being the
                   most effective
              Alternative Therapies
   Soy foods or isoflavone
    supplements - ? use in women
    with hx of breast cancer because
    of their estrogen effect. The most
    popular OTC tx presently.
   Black Cohosh – Clinical evidence
    mixed but trials ongoing. At this
    time the suggestive use of
    Remifemin 20mg – 2 tabs
    everyday
   Vitamin E – clinical evidence show
    mixed results. 800 IU/day
   OTC topical progesterone cream –
    not recommended due to content
    and concentrations differ widely in
    a variety of preparations and ?
    systemic effects.
   Also not recommended at this
    time is dong quai, evening
    primrose oil, ginseng, licorice,
    chinese herb mixtures,
    acupuncture or magnet therapy
           Vulvovaginal Changes with
                  Menopause
   Vaginal Dryness/Atrophic Vagnitis – Systemic hormonal therapy not
    recommended unless treating also moderate to severe vasomotor S/S or for
    osteoporosis prevention.

   First line treatment is vaginal lubricants that are water soluble and advise if
    possible regular sexual stimulation.

   Hormonal preparations:

        Vaginal Estrogen Rings – Estring & Femring are available with concerns
         with Femring for systemic effects. It is possilbe to use Femring for both
         vaginal therapy and systemic therapy. Ring last 90 days.
        Vaginal Estrogen Tablets –Vagifem, usual dose is 1x/day x 2 wks then
         2x/wk.
        Vaginal Estrogen creams – (Estrace or Premarin) 1x/day x 2 wks than 1-
         3x/wk.
        If using unopposed estrogen locally for long periods of time, yearly vaginal
         Ultrasound may be needed to assess the endometrium.
       Urinary Symptoms During
              Menopause
 Estrogen Therapy is not recommended with
  Stress or Urge incontinence. Clinical trials have
  shown no benefit.
 Assess for UTI, diabetes, drug interaction or
  cognition related phenomena if urinary
  symptoms present.
 Frequent UTIs can be due to lack of estrogen –
  only vaginal estrogen preparations have been
  proven to work with decreasing the frequency of
  UTIs in menopausal women.
 The HERS study showed no benefit with using
  systemic estrogens to treat reoccurring UTIs.
 North American
Menopause Society
   www.menopause.org

				
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posted:12/2/2011
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