Managing Menopause: Dealing With The Facts

1
Managing Menopause Dealing With The Facts

• Matt Weinrich, M.D.

2
Womens Top Health Risks and Causes of Death

• Perception
• Breast Cancer 46
• Other Cancer 16
• Heart Disease 4
• AIDS 4
• Uterine/Ovarian 3

• Reality
• Heart Disease 34
• Other Cancers 12
• Lung Cancer 5
• Stroke 8
• Breast Cancer 4

3
Chronic Diseases

• Screening can significantly reduce risk of
  cancer/heart disease
• The current challenge is dealing with nonfatal,
  chronic, age-dependent conditions such as
  Alzheimer's, osteoporosis, obesity, and
  incontinence
• Preventive health care should now be aimed at how
  a person can spend their many years as functional
  and productive ones

4
Menopausal Facts

• The time when the body quits making estrogen
• Average age 51
• Genetically determined
• Other factors involved smoking, underweight,
  high altitudes, vegetarian
• Not related to race, height, or age of first
  menses

5
Menopausal Symptoms

• Hot Flashes
• Vaginal dryness
• Sleep disorders
• Mood disturbances

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Hot Flashes

• Most common symptom of menopause
• Affects 68-93 of women
• Symptoms usually last 6 months to 5 years
• Primary reason women seek medical treatment
• 25 remain symptomatic for gt 5 years

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Severity of Reported Hot Flashes

• Severe 51
• Moderate 33
• Mild 16
• Symptoms decrease with time

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Hot Flashes Treatment

• Estrogen clearly the most successful (gt90)
• Decrease night sweats
• Decrease periods of wakefulness
• Increase REM sleep
• Stabilize mood

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Alternative Therapies for Managing Hot Flashes
Phytoestrogens

• Soy protein may decrease hot flashes
• Limited studies, mixed results
• Must be taken as pure soy protein
• No long term studies to show safety
• Dose is 20 grams pure soy protein once or twice
  daily

10
Alternative Therapies for Managing Hot Flashes
Red Clover

• One study showed 44 reduction
• Dose is 80 mg
• No long term studies

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Alternative Therapies for Managing Hot Flashes
Black Cohosh

• Short term studies show reduction by 70
• Dose is variable
• No study beyond 6 months

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Alternative Therapies for Managing Hot Flashes
SSRIs

• Selective serotonin reuptake inhibitors
• Decrease hot flashes by 50
• Effexor and Paxil the most well studied
• Reasonable option for women with breast cancer

13
Alternative Therapies for Managing Hot Flashes
Progesterone

• High dose progesterone reduces hot flashes by 25
  85
• High doses associated with weight gain
• Topical progesterone has not been well studied
• Topical absorption is variable

14
Alternative Medicine

• 42 of adults in 1998 used some form of
  alternative medicine
• 60 or 12 million paid cash
• 40 of patients do not inform their doctors
• Not regulated by the FDA
• Ingredients are not tested
• No scientific proof of benefits

15
Vaginal Dryness

• A very common complaint
• Generalized daily discomfort
• May result in pain with intercourse
• Primary treatment is oral or vaginal estrogen
• If fearful of systemic estrogen vaginal route
  effective with no major side effects
• Benefits noted in 2-4 weeks

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Osteoporosis

• 13-18 of Caucasian postmenopausal females have
  osteoporosis
• 30-50 have osteopenic
• 1998 1.5 million osteoporosis related fractures
• 13 billion dollars in health care services

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Osteoporosis

• Peak bone density is reached at around age 30
• 0.7 decline per year after that
• Potentially 5 per year for spinal bone following
  menopause

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Risk Factors for Osteoporosis Nonmodifiable

• Nonmodifiable
• Personal history
• Fracture in a first-degree relative
• Caucasian race
• Advanced age
• Female sex
• Dementia
• Poor health

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Risk Factors for Osteoporosis Modifiable

• Cigarette smoking
• Low body weight
• Estrogen deficiency
• Low calcium intake
• Alcoholism
• Impaired eyesight
• Recurrent falls
• Inadequate physical activity

20
Treatment of Osteoporosis with Estrogen

• Decreases fractures by 50 60 in arm and hip
  fractures
• Decreases up to 80 of vertebral compression
  fractures
• Requires beginning within 5 years of menopause
• Protective effect lost rapidly after therapy
  ended

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Alternative Therapies for the Treatment of
Osteoporosis Bisphosphonates

• Binds to bone to prevent resorption
• Reduces nonvertebral fractures by least 30
• Reduces vertebral fractures by 90
• Can be added to estrogen for combined effects
• Side effects are minimal
• Taken with a full glass of water and remain
  upright for 30 minutes without food or beverage
• Do not lose effect after discontinued

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Alternatives for Osteoporosis Selective
Estrogen Receptor Modulators (SERMs)

• Synthetic agents
• Beneficial effects on bone and cholesterol while
  decreasing the risk of breast cancer and
  endometrial cancer
• Similar to estrogen in regards to bone
• Full benefits currently under study
• Increase severity of hot flashes

23
Colorectal Cancer and Estrogen

• Third most common cancer
• significantly decreases risk with current and
  long term use
• Most studies show a decrease by 35
• Reason for the benefit is unknown

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Estrogens Benefits and Mental Health

• Sleep disturbances
• Energy
• Cognitive function
• Sexual impairment
• Decreased depression on most depression scores
• Overall increased sense of well-being

25
Estrogen and Alzheimer's Disease

• Mixed studies
• Possible decrease in Alzheimer's by 80
• Longer treatment more beneficial
• Estrogen increases cerebral blood flow
• Not helpful once disease is established

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Other Benefits of Estrogen

• Less risk of diabetes
• Decreased body fat
• Decreased arthritis
• Decreased tooth loss by 25
• Decreased vision and hearing loss

27
Estrogens Types, Delivery Systems, and Regimens

• There are a variety of estrogens
• Primarily estradiol and estrone
• All estrogens have similar ability
• Impact on bone mineral density
• Hot flashes

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Oral Route Advantages

• Most common
• Must be absorbed through the GI tract
• Increases HDL cholesterol
• Decreases LDL cholesterol
• Decreases some blood clotting factors
• These have been shown to decrease the risk of
  cardiovascular disease

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Oral Route Disadvantages

• Increase in triglycerides
• Larger doses required than the patch
• Small risk of GI irritation and nausea
• Increases plasminogen (a blood clotting factor)

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Patch Advantages

• Once or twice per week
• Good choice for those who cannot take pills
• No impact on triglyceride levels
• Equal to oral forms in regards to bone protection
• Potentially safer with a steady state release

31
Patch Disadvantages

• Occasional rash from adhesive
• May require progesterone
• Combination estrogen/progesterone patch is larger
  than the estrogen patch

32
Estrogen Vaginal route

• Easily absorbed for local therapy
• Effective for vaginal dryness and painful
  intercourse
• Three options for vaginal route exist
• Creams messy, dosing less precise, absorbed
  systemically
• Tablets twice weekly, minimal absorption
• Vaginal ring 3 month dosing

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Contraindications to Hormone Therapy

• Pregnancy
• Breast cancer
• Estrogen-dependent cancer
• Abnormal genital bleeding
• Blood clots
• Active liver disease

34
Estrogen and Blood Clots

• A twofold increase in the risk of blood clots
  with hormone therapy
• Confined to the first 2 years
• Amounts to an increase of 1.5/10,000 per year
• Risk of death is very low

35
The Womens Health Initiative

• Exaggerated in the popular media
• Caused fear and confusion in American women
• No one study has changed the publics opinion in
  gynecology

36
WHI and Breast Cancer

• Cited an increased of 26
• 8/10,000 cases per year
• Was not statistically significance
• The estrogen only group was not stopped
  prematurely because of an increased risk
• It takes 10 years for a malignant cell to become
  clinically detectable at 1 cm
• Increased risk in years 4 and 5 consistent with
  hormonal stimulation of preexisting tumors

37
Breast cancer

• Over 50 100 studies linking hormone therapy and
  breast cancer
• Only a few studies shown a small increased risk
• Ever use 1.14
• Current use 1.24
• Past use 1.07
• No study links hormone therapy with a positive
  family history

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Mortality from breast cancer when using HRT at
the time of diagnosis

• The majority of studies have shown a decreased
  risk of dying from breast cancer when on HRT
• Breast cancer in users of HRT appear to be
  different compared to nonusers
• Smaller tumor size
• More differentiated
• Less spread to lymph nodes
• Less likely to be invasive

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WHI and Cardiovascular Disease

• WHI was labeled as a primary prevention trial
• Debated by average of the participants
• 45 were in their 60s
• 21 in their 70s
• Implies that the majority of patients were
  already at risk

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WISDOM

• International British study involving 34,000
  women ends this year to evaluate HRT and it
  effects on
• Fatal and nonfatal ischemic heart disease
• Major osteoporotic fracture
• Breast cancer
• Quality of life
• The study was not stopped prematurely because the
  researches felt that the WHI study was not
  statistically significant

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Estrogen Risks/Benefits

• Evidence to show a small increased risk of
  cardiovascular disease and breast cancer
• Evidence to support HRT in decreasing symptoms
  such as hot flashes, vaginal dryness, and sleep
  problems
• Evidence to show HRT decreases osteoporosis and
  colorectal cancer
• Evidence to support other benefits of HRT
  including improved cognition, decreased
  Alzheimer's disease, urinary incontinence, and
  tooth loss

42
Reasonable Alternatives

• Hot flashes herbal regimens may help, SSRIs
  have shown significant benefit
• Vaginal dryness vaginal rings, creams and
  tablets with minimal absorption
• Osteoporosis SERMs and Bisphosphonates decrease
  bone loss
• Cardiovascular disease cholesterol lowering
  agents statins decrease the risk of
  cardiovascular disease

43
Conclusion

• Determine what is important to you
• Evaluating your goals may make more options
  available
• Focus on the best way to live a healthy and
  active life

44
Alternatives to osteoporosis SERMs

• Works similar to estrogen in regards to bone loss
• Has been shown to increase bone in spine and
  femoral neck
• Reduced risk of vertebral fractures by 36
• No decrease in hip or nonvertebral fractures
  noticed

45
Cognition

• Limited data exists that shows women have better
  memory while on estrogen
• Estrogen has been shown to promote brain health
  by increasing cerebral blood flow
• On going trials are being performed that suggest
  estrogen long term may decrease Alzheimer's by
  50

46
Phytoestrogens

• Nonsteroid compounds that bind to the estrogen
  receptor
• The most common are isoflavones which possess
  both estrogenic and antiestrogenic properties
• Phytoestrogen rich diet is cited as a factor in
  the low incidence of breast cancer and
  cardiovascular disease among Asians

47

• Phytoestrogens have mixed results in the
  literature in regards to alleviating the symptoms
  of menopause
• There are been equal studies, some showing
  benefit while other show no benefit in regards to
  hot flashes, libido, vaginal dryness, after 3
  months

48

• In regards to cardiovascular disease
  phytoestrogens have been shown to decrease LDL
  cholesterol
• This requires the intact soy protein
• Separation of the isoflavone from the protein has
  been shown to have no benefit from placebo

49

• Small amount of evidence shows that
  phytoestrogens may prevent bone loss
• This was only vertebral bone
• Hip bone was not affected
• Overall benefit significantly less than estrogen
  or SERMs

50
Progesterone topical

• Progesterone used twice daily has been shown to
  have no effect on bone density, cholesterol
• Transdermal progesterone has been shown to have
  little systemic absorption and great serum
  variability

51

• The average age of US women at menopause is 51
  years
• Most women spend at least one third of their
  lifetime in the postmenopause
• 1.3 million women reached natural menopause
  during 2000
• Induced menopause occurs at a rate of 4,900 women
  per day

52

• Menstrual irregularities usually begin at age 40
• Only about 10 of women have normal menstrual
  cycles from age 40 until menopause
• It is not a declining level of estrogen that
  causes menstrual cycle irregularities, but
  depletion of eggs that the ovary can produce
• It has been shown that estrogen levels are higher
  just before menopause and some experts theorize
  this is to extend the benefits of estrogen before
  menopause begins

53

• Studies have shown that even if there is an
  increased risk of breast cancer the cancer is
  localized to the breast and associated with
• Earlier detection
• More well-differentiated tumors
• Better survival when compared to nonusers of
  hormone therapy
• Mortality rates are reduced in users

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• Menopause is not a disease
• Can be looked at as a signal of revival and
  renewal for the better
• We should consider is a landmark to focus on at
  least 30 years of active, healthful living.

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• There are more older people in the United States
  than ever before
• Year population over 65 of pop
• 1900 3 million 4
• 2000 34 million 12
• 2030 58 million 20

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• Along with this increase is an increase in the
  female percentage of the population
• Year men women ratio
• 1900 102100
• 2000 23 in the over age 65 age group
• 13 in over 85 age group
• The death rate is higher for men for both medical
  and nonmedical reasons including cardiovascular
  disease, lung cancer, accidents, suicide,
  smoking, alcohol consumption, and higher risk
  taking behaviors

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Midlife Assessment Emphasis of prevention

• Beginning in the menopausal years is the ideal
  time to focus on preventative care and long term
  thinking with three primary goals
• Prolong maximal physical, mental, and social well
  being
• Surveillance for major chronic diseases
• To help smooth the passage from reproductive to
  menopausal years

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• Other periodic tests may include
• Fasting glucose
• Thyroid
• Kidney function testing
• Osteoporosis screening
• Immunization status cannot be undervalued for the
  elderly and may include
• Pneumococcal
• Influenza
• Diphtheria-Tetanus
• Hepatitis

59

• Preventative screening may include the following
• Height, weight, and blood pressure
• Annual breast exam
• Annual pap smear screening
• Cholesterol screening every 3 -5 years
• Colorectal screening annually to every 10 years
  depending on the screening technique

60

• Increasing exercise and muscle mass has also been
  shown to improve strength and balance and reduce
  falls which may threaten a persons independence

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Basics of Postmenopausal Hormone Therapy

• The first test of hormone therapy to reduce the
  effects of aging dates back to 1889
• Estrogen and Progesterone were isolated and
  synthesized in the 1930s
• Hormone replacement was approved for use in 1942
• 1970 the side effect of endometrial cancer was
  identified as a major health concern for those on
  estrogen

62

• Progestin was added to eliminate the risk of
  endometrial cancer and soon it became one of the
  most commonly prescribed medications in the US
• Now with the recent published report of the Women
  Health Initiative hormone replacement again has
  been criticized by many

63

• The MORE study also evaluated breast cancer risk
  on SERMs
• Results of study showed a reduced incidence of
  newly diagnosed invasive breast cancer by 72
• Estrogen receptor breast cancer was reduced by
  84
• Longer term studies are needed to fully evaluate
  the overall benefits of SERMs

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Cardiovascular disease

• Major risk factors
• Hypertension
• Smoking
• Diabetes
• obesity
• Men are 3 times more likely to die of heart
  disease until women reach menopause
• Observational data points to estrogen as the
  protective agent

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Estrogen role in cardiovascular disease

• Reduces LDL cholesterol
• Raises HDL cholesterol
• Decreases blood clotting factors
• Together both serve to decrease plaque formation
  within the blood vessel wall
• While the addition of a progesterone may decrease
  the HDL affect there should be no other changes
  noticed

66

• Although there appears to be a role for primary
  prevention this is not true for secondary
  prevention
• two large studies suggest that women taking
  hormone therapy with known heart disease may have
  increased risk of heart attack in the first two
  years

67

• Endometrial cancer
• It is well known that estrogen without
  progesterone is associated with endometrial
  cancer
• Addition of progesterone negates the risk

68

• Endometrial cancer
• It is well known that estrogen without
  progesterone is associated with endometrial
  cancer
• Addition of progesterone negates the risk

69

• Follow up was not long enough to provide outcomes
  of the breast cancer in the participants

Oral Route Advantages
70

• Creams
• Dosing less precise
• Messy
• Can be absorbed systemically so progesterone is
  required for an intact uterus
• Ring left in place for 3 months, systemic
  absorption not significant
• Tablets twice a week maintenance dosing, little
  systemic absorption
• All can be used with patients who have liver
  disease, inability to tolerate side effects of
  systemic hormone, and do not adversely affect
  cholesterol

71

• Creams
• Dosing less precise
• Messy
• Can be absorbed systemically so progesterone is
  required for an intact uterus
• Ring left in place for 3 months, systemic
  absorption not significant
• Tablets twice a week maintenance dosing, little
  systemic absorption
• All can be used with patients who have liver
  disease, inability to tolerate side effects of
  systemic hormone, and do not adversely affect
  cholesterol

• Osteoporosis

72
Prevention and Treatment with Estrogen

• Inhibits bone resorption
• Promotes absorption of calcium
• Increased vitamin D
• Conserves calcium lost from the kidneys
• Increases the survival of the cells that form new
  bone
• Estrogen is primary prevention for osteoporosis

73

• Bisphosphonates are only indicated for bone loss
  and has no other benefits
• Unlike estrogen, they do not lose effect after
  discontinuation

74
Alternatives to osteoporosis

• SERMs
• Multiple outcomes of Raloxifene Evaluation (MORE)
  trial was performed to evaluate Raloxifene on
  osteoporosis fractures
• At 3 years vertebral fractures was significantly
  reduced
• Did not show protective benefit of hip fractures
  when compared to placebo
• Did increase femoral neck bone mineral density
  by over 2 over the 3 year trial

75

• SERMs unfortunately have been shown to increase
  the frequency and severity of hot flashes

76
WHI and Breast Cancer Continued

• WHI study results on breast cancer did not
  actually reach statistical significance
• A analysis of 51 studies from the world
  literature found a 14 increased risk in
  ever-users, but no increased risk associated with
  past use or family history
• This disease was localized to the breast

77
Lifestyle adjustments

• Cigarette smoking the single most preventable
  cause of illness and death in the US since 1970
• Possibly worse for women than men
• 1-4 cigarettes per day increases risk of death
  from heart disease by 2.5X
• Increases other chronic diseases such as
• stroke
• osteoporosis
• pulmonary disease
• cervical and bladder cancer
• Alzheimer's
• worsens cholesterol
• urinary incontinence
• tooth loss

78

• Alcohol use in moderation (1-2 drinks/day) has
  been shown to decrease heart disease by raising
  HDL cholesterol
• Greater than 2 drinks/day has been shown to
• damage heart muscle
• alter heart rhythm
• constrict blood vessels
• raise blood pressure
• increase risk of stroke and liver disease
• increase the risk of osteoporosis
• Minor effects also include worsening of hot
  flashes, interfere with sleep patterns, and
  exaggerate emotional stress

79

• Physical activity the magic cure has clearly
  been shown to
• lower blood pressure
• reduce weight
• slow bone loss
• build muscle mass
• overcome insomnia
• relieve stress
• lower risk of heart disease
• Stroke
• Diabetes
• high cholesterol
• Ulcers
• pulmonary disease
• breast and reproductive cancers

80

• Minimal cardiac fitness is 30 minutes 3 days/week
• New information shows that optimal fitness is
  obtained with 1 hour 5-7 days/week
• Nurses health study showed that brisk walking for
  3 or more hours a week decreased the risk of
  heart attacks by 30-40
• Only weight bearing exercises can increase bone
  density

81
Nutrition

• 20-30 of women beyond age 30 are more than 20
  overweight
• Women have more problems with weight loss because
  of a decreasing metabolic rate with age
• Recommended calcium intake is
• 1000mg for premenopausal/women taking estrogen
  1500 mg for women over 65 not on estrogen
• Vitamin D 400IU is also required for optimal
  absorption of calcium