MENOPAUSE

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MENOPAUSE

• 40 million menopausal women in the U. S. presently

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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.

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DIAGNOSIS

• A womans 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 gt 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 FSHLH
  ratio looking for gt than 1 or estradiol lt than 20
  pg/ml on the 7th pill free day.
• Always remember thyroid disease can mimic
  menopause, a TSH measurement may be necessary.

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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.

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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 womens risk of
  vaginal and urinary tract infections, and also
  urinary incontinence.

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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.

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Do You Treat with Hormonal Therapy???

• The Womens 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.

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Womens 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.

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• 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.

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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.

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• 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.

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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.

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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

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Estrogen/Progesterone Preparations for
Postmenopausal Use

• Continuous combined has decrease rate of
  breakthrough bleeding and fewer endometrial bx
  than cyclic regimen.

• Continuous combined Prempro
• Continuous Cyclic Premphase
• Intermittent Combined Prefest
• Transdermal Continuous Combined - Combipatch

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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.

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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
• SSRIs being the most effective

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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

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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.

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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.

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North American Menopause Society

• www.menopause.org