Midlife and Beyond 2004

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Mid-lifeand Beyond

• By Green Hsueh, M.D., F.A.C.O.G.

3
Midlife

• The midpoint in an individuals life, or the time
  when an individual is no longer considered young
  but is not ready for retirement. (Leggett, 2007,
  Bennett Flaherty-Robb, 2003)
• In 1796, the average life span was 25 years.
• In 1896, the average life span almost doubled to
  48 years.(Katz GoldmanThe New Anti-aging
  Revolution ,2002)

4
CAN WE LIVE LONGER?Los Angeles Times Dec.25,2006

• The Average U.S. Life Expectancy has been
  increasing for more than 100 years and hit a
  record high in 2004
• 80.4 years for women
• 75.2 years for men

5
Centenariansthe fastest-growing segment of the
population.(LA Times Dec.25, 2006)

• In developed countries, the numbers of people
  over 100years of age have been doubling every
  five to seven years.

6
The aging baby-boomers

• U.S. persons age 65
• 34.835 millions in 2000
• 70.319 millions in 2030
• As seniors live longer, they face much greater
  risks of disease and disabilities.

7
Human Life Span

• Today, human life expectancy has been steadily
  increasing by about 2.2 months per year.
• This progress has been steady for at least the
  past 60 years.
• (Grossman T Keio J Med 2005)

• The maximal life span is still probably somewhere
  between 100 and 120 years.
• (Roth G. JAGS 2005)

8
Anti-aging interventions

• Current interest is fueled by the appeal of its
  promises to baby boomers trying to preserve their
  youthfulness as they approach chronological old
  age and older persons attempting to rejuvenate
  themselves.
• Mehlman mJ, Binstock RH et al, The
  gerontologist 44,2004

9
Average American Womans Menstrual Cycle

• Menarche
• 12.6 years
• Menstrual Interval
• 21 to 44 days
• Menopause
• 51.4 years

10
Womans life expectancy

• The average American womens life expectancy
  currently exceeding 81 years of age.
• Most women can expect to live more than one third
  of their lives well beyond their child-bearing
  years.

11
Female Reproductive System
12
Major Sex hormones

• Female
• Estrogen
• Progesterone

• Male
• Testosterone
• DHEA

13
Definition of Menopause

• Natural the permanent cessation of menses from
  loss of ovarian follicular function
• Surgical Cessation of menstruation produced by
  artificial means ( ie, surgical removal of
  ovaries)
• Result ifs a gradual(natural) or sudden
  (surgical) condition of estrogen deficiency.
• Nachtigall LE, Womens
  Health Forum 2007

14
Feminine Foreverby Robert A Wilson M.D., 1960

• Estrogen could keep women energetic,
  young-looking and straight-backed into old age.
• The benefits of hormone therapyto combat the
  tragedy of menopause

15
Menopausal-Related Changes

• Skin changes
• Vasomotor symptoms
• Sleep quality
• Urogenital symptoms
• Sexual well-being

16
What is skin aging?

• Older skin has decreased amounts of collagen,
  elastin, and hyaluronic acid.
• 30 of skin collagen is lost in the first 5 years
  after menopause with an average decline of 2.1
  per postmenopausal year during a period of 20
  years.
• Brincat M et al. Br. Med J ( Clin Res. Ed) 1983

17
Skin Aging

• Aging skin loss of elasticity, reduction in
  epidermal thickness, and elastic degeneration.
• The loss of estrogen causes skin collagen level
  to decrease markedly in the initial
  postmenopausal years.
• Collagen level increased in estrogen treatment.
• Estrogen preserves elastic properties and skin
  thickness.
• Pieced GE,1995, Brincat M. Et al,1985

18
Hormone Therapy and Skin Aging

• Long-term hormone therapy in postmenopausal
  women is associated with significantly fewer
  wrinkles and less skin rigidity.
• Wolff ER, Narayan D., Taylor. H Fertility and
  Sterility 84 (2), Aug 2005

• Topical and oral estrogens are beneficial in
  maintaining skin firmness and elasticity in
  postmenopausal women.
• Draelos, ZD, Fertility and Sterility 84 (2),
  Aug.2005

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What can be done to prevent skin aging?

• Long-term hormone replacement therapy helps
  prevent skin aging.
• Sunscreens, retinoids, and oral or topical
  antioxidants should also be used.
• Leslie BaumannA dermatologists opinion on
  hormone therapy and skin aging, Fertility and
  Sterility, Aug 2005

20
Consequences of Estrogen on Target Tissue
CNS Effects Hot flashes Sleep
disturbance Mood Libido Cardiovascular Breast Oste
oporosis
Brain
Eyes
Vasomotor
Heart
Bone
Breast
Colon
Urogenital Tract
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Vasomotor Symptoms

• Hot flashes
• Night sweats

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Vasomotor Symptoms

• Hot flushes 24 to 94 postmenopausal, 10 to
  25 premenopausal women.
• Variable in frequency, duration and intensity.
• Prevalence highest in the 2 years after
  menopause, decreases within 7 years.

• Variety of possible causesmenopause, thyroid
  abnormalities, leukemia's, and pancreatic tumors.
• Estrogen therapymost effective.

23
Insomnia
24
Reanalysis of the WHIMS study Victor W.
Henderson, M.D., M.S. et al, (Stanford
university),BOSTON, May 3,2007

• The new analysis suggests that women who used
  estrogen may have a nearly 50 lower risk of
  Alzheimer's, as long as they began using the
  hormone before age 65

• American Academy of Neurology 2007 Annual
  Meeting,
• Women who took estrogen before age 65 may not be
  at a higher risk of later dementia after all.

25
Atrophic Changes

• Vaginitis
• Urethritis
• Bladder dysfunction

26
Hormonal Replacement Therapy Improves Sexual
Function
100
90
90
80
70
52
60
Improved
42
50
40
30
30
30
20
10
0
Sensitivity
Orgasm (frequency)
Desire
Behavior
Orgasm (intensity)
Yale Mid-Life Study.Sarrel PM. Obstet Gynecol.
199075263-303.
27
Sexual function

• Androgens are essential in the stimulation and
  maintenance of sexual function in men (and
  probably in women).
• F.Jockenhovel, The Aging Male 20047319-324

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Testosterone Patch Helpful for Women With
Androgen Deficiency and Hypopituitarism 

• During testosterone administration, mean free
  testosterone increased into the normal range.
  Compared with the placebo group, the testosterone
  group had increases in mean bone mineral density
  in the hip (P .023) and radius (P .007), but
  not in the posteroanterior spine. The
  testosterone group also had increases in mean
  fat-free mass (P .040) and thigh muscle area (P
  .038), but not in fat mass and improvements in
  mood (P .029), sexual function (P .044), and
  some aspects of quality of life, but not
  cognitive function. At physiologic replacement
  levels, testosterone was well tolerated, with few
  adverse effects.(KK Miller et al, J Clin
  Endocrinol Med. 2006911683-1690 )

29

• Osteoporosis
• A condition of skeletal fragility characterized
  by reduced bone mass and microarchitectural
  deterioration

Normal Bone
Osteoporosis
World Health Organization. Guidelines for
Preclinical Evaluation and Clinical Trials in
Osteoporosis. Geneva, Switzerland World Health
Organization 1998.
30
Bone loss affects both men and women

• Women can lose up to 20 of their bone mass in
  the five to seven years following menopause,
  making them more susceptible to osteoporosis.
• NIH Osteoporosis and Related DiseasesNational
  Resource Center 10/00

• Men also develop osteoporosis, but generally
  later than women. By age 65 or 70, women and men
  loose bone mass at the same rate, and dietary
  calcium absorption decreases for both sexes.

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50 and older

• 1 in 2 women will suffer an osteoporosis-related
  fracture in her lifetime
• Men have an estimated lifetime risk of hip, spine
  or distal forearm fracture of 20.7. However, men
  account for about 30 of all hip fractures.
• van Staa TP et al 2001, Cooper C et al.1992

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Osteoporosis Symptoms

• The silent disease-Bone loss occurs without
  symptoms
• Collapsed vertebrae-severe back pain, loss of
  height,or spinal deformities. 2/3 spine fractures
  occur without symptoms
• Bones become so weak that a sudden strain, bump,
  or fall causes a fracture.
• NIH Osteoporosis and Related Bone
  DiseasesNational Resource Center

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Osteoporosis Risk Factors You Cannot Change

• Gender being female
• Body size thin or small frame
• Age
• Family history of osteoporosis
• Ethnicity Caucasian and Asian women at highest
  risk Latino and African-American at lowest risk
• Previous fracture Women with preexisting
  vertebral fractures had approximately 4 times
  greater risk of subsequent vertebral fractures
• NIH Osteoporosis and Related Bone
  DiseasesNational Resource Center 10/00
• Klotzbuecher CM, et al. J Bone Miner Res.
  200015(4)721727

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Osteoporosis Risk FactorsYou Can Change

• Sex hormones abnormal absence of menstrual
  periods (amenorrhea), low estrogen levels
  (menopause), low testosterone levels in men
• Eating disorders anorexia nervosa or bulimia
• Diet low in calcium
• Certain Medications, such as corticosteroids and
  anticonvulsants
• Inactive lifestyle or extended bed rest
• Cigarette smoking
• Excessive use of alcohol
• NIH Osteoporosis and Related Bone
  DiseasesNational Resource Center 10/00

35
Therapeutic Options

• Antiresorptive Therapy
• Hormone replacement therapy (HRT)
• Raloxifene (Evista)
• Bisphosphonates
• Alendronate (Fosamax)
• Risedronate (Actonel)
• Calcitonin (Miacalcin)

• Anabolic Therapy
• Parathyroid hormone (PTH)

36
ERT/HRT and CVDSummary of Observational Studies
Relative Risk
Stampfer et al, 1985
Bush et al, 1987
Petitti et al, 1987
Boysen et al, 1988
Criqui et al, 1988
Henderson et al, 1988
van der Giezen et al, 1990
Wolf et al, 1991
Falkeborn et al, 1992
Psaty et al, 1994
Folsom et al, 1995
0
0.5
1.0
2.0
10
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The Womens Health InitiativeIts Good, Its
Bad and Its Ugly

• 1993-1998 enrolled 27,000 women
• Scheduled to conclude in 2005
• 16,608 healthy menopausal women randomized to
  combination CEE/MPA vs placebo
• Mean follow up of 5.2 years (range 3.5-8.5
  years)
• Aged 50-79 with a mean of 63.3 7.1 years
• 45 were in their 60s and 21 in their 70s

The Writing Group for the WHI Investigators JAMA
2002288321-333.
38
The Impact of the Womens Health Initiative on
the Perimenopausal Patient

• Women enrolled in the WHI did not mirror HT
  candidates in actual clinical settings.( Average
  age 63 years the majority were years into
  menopause, and most had never used hormones)

• The WHI did not include perimenopausal women,
  but the results have had a profound impact on
  them..
• Patricia J Sulak, The Female patient3112,
  Dec.2006

39
WHI Results (JAMA 2002)Absolute and Relative
Risk or Benefit of HRT
40
WHI Estrogen Progestin Trial Summary

• CEE 0.625mg/dMPA 2.5 mg/d should not be
  initiated or continued for the primary prevention
  of CVD
• Risks for early harm for CVD. Continuing harm for
  stroke and VTE, and increasing harm for breast
  cancer.
• National Heart Lung, and Blood Institute 2002

• Treatment with estrogen plus progestin for up to
  5 years is not beneficial overall.
• Risks for CVD and breast cancer must be weighed
  against the benefit for fracture and colon cancer
• This trial did not address the use of estrogen
  plus progestin for short-term relief of
  menopausal symptoms.

41
The Womens Health Initiative

• 97.5 of women had no events
• There were no differences in mortality or cause
  of death between groups.
• The previously summarized Hazard risks amount to
  an extremely small increase in absolute risk
• 7 additional myocardial infarctions per 10,000
  person years
• 8 additional strokes per 10,000 person years
• 8 additional breast cancers per 10,000 person
  years
• 18 additional PE/DVT per 10,000 person years

The Writing Group for the WHI Investigators JAMA
2002288321-333.
42
Breast Cancer Risks for Women
43
Changing RisksHow the disease risks of hormone
users may differ from the risks of non-users.
Source Womens Health Initiative, The Wall
Street Journal, July 13, 2004
44
Estrogen Use After Menopause Does Not Increase
Breast Cancer Risk

• (Reuters Health) - Seven years of treatment with
  conjugated equine estrogen (CEE) in
  postmenopausal women with prior hysterectomy does
  not raise the risk of breast cancer, and may in
  fact reduce the risk, according to a detailed
  analysis of data from the Women's Health
  Initiative (WHI) Estrogen-Alone trial.

45
Effects of conjugated equine estrogens on breast
cancer and mammography screening in
postmenopausal women with hysterectomy. (Marcia
L. Stefanick et alJAMA April 12.2006295)

• CEE appeared to exert a protective effect in
  women with a lower 5-year Gail Risk Score (p
  0.01), benign breast disease (p 0.005), and
  those with no first-degree relatives with breast
  cancer (p 0.01).

• After adjusting for adherence in which follow-up
  was censored 6 months after treatment
  discontinuation, there was a larger and
  significant reduction in the incidence of
  invasive breast cancer in the CEE group (HR
  0.67, p 0.03).

46
U.S. breast cancer rates dropped 7 in 2003

• 14,000 fewer breast cancer diagnosed in 2003 than
  in 2002. (gt200,000 cases each year) study funded
  by the National Cancer Institute and the M.D.
  Anderson Cancer center, Dec. 2006
• Prescriptions for estrogen and progestin fell by
  almost half in mid-2002.
• It was not clear whether discontinuation of
  hormone therapy completely stopped very small
  cancers from growing or merely slowed them down
  so they remained undetectable. (Dr. Peter Ravdin,
  a study co-author)

47
Rethinking Hormones Again Heart Risk May Be
Lower in Women Who Start Early The Wall Street
J, by Tara Parker-Pope, quoting Dr. Francine
Grodstein, Harvard Medical School
Years after menopause that therapy was begun Heart risk
0 to 9 -11
10 to 19 22
20 or more 71
48
Conjugated Equine Estrogens and Coronary Heart
Disease--The Womens Health Initiative (Arch
Intern Med. 2006 )

• Conjugated equine estrogens provided no overall
  protection against myocardial infarction or
  coronary death in generally healthy
  postmenopausal women during a 7-year period of
  use.

• There was a suggestion of lower coronary heart
  disease risk with CEE among women 50 to 59 years
  of age at baseline.

49
Hormone Therapy and Dementia

• Women enrolled in the WHIMS trial were 65 to 79
  years of age at the time of randomization, and
  without dementia.
• Neural consequences of HT could differ between
  younger and older women.
• Henderson VW, the Female Patient, Vol.30, Jan 2005

• Womens Health Initiative Memory Study (WHIMS)
  The risk of dementia was 76 greater for women
  randomized to receive HT.

50
Alzheimer disease

• The most common cause of dementia
• Prevalence higher in women Rare before
  menopause
• 5 between ages 65 and 74 years, 17 between ages
  75 and 84 years, and 46 for ages 85 years and
  older
• Hebert et al, 2003

51
Effects of Estrogen on the Brain

• Estrogen is involved in regulation of neural
  connections, both developmentally and during a
  womans menstrual cycle.
• Loss of Estrogen may cause the weakness in
  short-term verbal memory

• Estrogen regulates cerebral blood flow-supplying
  nutrients and carrying away waste products.
• Estrogen is a powerful antioxidant.
• Estrogen may play a role in immune regulation.
• Naftolin F 3rd Yale Conf on Womens Health
  Fitness2000

52
Estrogen and CNS Functions

• Cognition
• Sleep
• Mood
• Stress
• Alzheimers Disease?

53
New Analysis Reverses Thinking on Estrogen and
Alzheimer's Victor W. Henderson et al, May 2007

• The original WHIMS study 2003
• Both estrogen alone and estrogen plus progestin,
  were associated with increased risk for dementia.

• Current reanalysis 2007
• Prior estrogen use was associated with a lower
  risk of Alzheimer's dementia, but non-Alzheimer's
  dementia risk was not significantly reduced by
  hormonal therapy.

54
Hormones and Gallbladder diseases

• Postmenopausal women who use conjugated equine
  estrogens (CEE) or estrogen plus progestin are at
  increased risk of biliary tract disease,
  according to findings from a randomized trial of
  healthy women. The elevated risks ranged from 54
  to 93 depending on the estrogen and disease
  type.
• Wallace
  RB et al,JAMA 2005293330-339.

55
Colon Cancer

• The risk of colon cancer is reduced by
  approximately half for women who used HRT
  recently
• Risk cessation is maintained for about 10 years
  after cessation of use

Peter JD 1995
56
WHI and aftermath looking beyond the figures

• The panic over hormone treatment for menopausal
  women was unjustified.
• The data for women younger than 60-years-old was
  reassuring.
• Amos Pines, Maturitas-the European Menopause
  Journal 51 (2005)

57
Andropause (Male Menopause)

• Most men begin to experience changes in their
  bodies somewhere between the ages of 30 and 55.

• The symptoms tend to come on slowly and
  gradually, creeping up over a period as long as
  20 years.
• Alan P . Mints http//totalhealthmagazine.co
  m

58
Aging Man in the U.S. 65 or older

• 2000
• 34.0 million U.S. residents age 65 or older,
  12.7 million men

• 2050
• 86.6 million U.S. residents age 65 or older,
  38.2 million men

59
Androgen Decline in Aging Men

• Male menopause
• Male climacteric
• Andropause
• Androgen decline in the aging male--ADAM
• Late-onset hypogonadism--LOH

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Typical symptoms of late-onset hypogonadism

• Diminished libido
• Erectile dysfunction
• Fatigue
• Irritability
• Sleep disturbances
• Changes in mood and intellectual function

• Decreased lean body mass
• Visceral (abdominal) obesity
• Decreased muscle strength
• Osteopenia
• Osteoporosis
• (Mahmoud A and Comhaire FH Nature clinical
  practice/Urology, Aug, 2006)

61
St. Louis University Androgen Deficiency in Aging
Male (ADAM) questionnaire Haren et al. Med Clin
N Am 90 (2006)

• 7. Are your erections less strong?
• Have you noticed a recent deterioration in your
  ability to play sports?
• Are you falling asleep after dinner?
• . Has there been a recent deterioration in your
  work performance?

1. Do you have a decrease in libido (sex drive)?
2. Do you have a lack of energy?
3. Do you have a decrease in strength and/or
   endurance?
4. Have you lost height?
5. Have you noticed a decreased enjoyment of life?
6. Are you sad and/or grumpy?

62
Risk Factors for Andropause

• Most frequent age for onset of symptoms 51-60
  years
• Next most common age 61-70 years

• Smoking more than 10 cigarettes a day was
  independently associated with an earlier onset
  (lt50 years) of andropause symptoms.
• No association with ethnicity or alcohol

Tan RS, Philip RS 1999
63
Age related testosterone level and male
andropause syndrome

• Serum total testosterone levels were measured in
  53 symptomatic men older than age 50 and 48 men
  younger than age 40 for a control group
• The mean testosterone level for symptomatic men
  older than age 50 (2.68/-0.51ng/mL) was
  significantly lower than control group
  (7.01/-0.82ng/mL).

Wu CY, Yu TJ, Chen MJ Changgeng Yi Xue Za Zhi
2000 Jun 23 (6) 348-353
64
Aging Males Symptoms and Hormone levels

• Partial androgen deficiency of the aging male
  PADAM-related symptoms as evaluated by the AMS
  Scale are not significantly related to serum
  leves of TT, FT, E2, LH, FSH, DHEA-S, or GH.
• Miwa Y, Haneda T. Yokoyama O, Fukui, Japan J
  Sex Med 2006

65
Testosterone treatment

• Even though serum total and free testosterone
  concentrations fall with increasing age, we do
  not yet know if increasing the serum testosterone
  concentrations of elderly men will prevent or
  reverse these changes.
• Potential harmful effects ?Prostate
  cancer/hyperplasia, sleep apnea, erythrocytosis,
  serum lipid abnormalities.
• Peter J Snyder, 2005UpToDate

66
Andropause, Testosterone Replacement Therapy for
Aging Men

• Physicians should consider hypoandrogenism if
  male patients complain of loss of libido,
  erectile dysfunction, weakness, fatigue,
  lethargy, loss of motivation, or mood swings
• Most men treated with testosterone will feel
  better

Bain J., Can Fam Physician 2001 Jan 4791-7
67
Treatment of the Aging Males symptoms

• After 1998 (the introduction of
  sildenafil-Viagra), using Self-Report
  Questionnaires may result in compressing the
  clinician-patient dialogue, standardization of
  sexual life and misdiagnosis and treatment.
  (Tiefer L. 2006)

• Testosterone replacement can reverse many
  deficiency effects. At present, no ideal form of
  testosterone replacement is available. is a
  quality of life issue.(Haren et al. 2006)

68
The New View Approach to Mens Sexual Problems

• Sexual problems Discontent or dissatisfaction
  with any emotional, physical, or relational
  aspect of sexual experience
• Tiefer L, Medscape July 26,2006, (The New
  View Working Gr. Morin J Klein M et al)

1. Sociocultural, political or economic factors
2. Partner and relationship
3. Psychological factors
4. Physiologic or medical factors

69
Anti-aging Market in the United Statesa research
report prepared by FIND/SVP

• 43 billion in 2002
• 64 billion in 2007

70
Alternatives to Hormones

• Osteoporosis
• Lifestyle changes (diet, exercise, stop smoking,
  etc.)
• Bisphosphonates (Fosamax, Actonel,Boniva.)
• Selective estrogen receptor modulators
  (SERMs)-Raloxifene(Evista)
• Calcitonin( Miacalcin )

• Vasomotor symptoms
• Lifestyle changes, cool environment
• Antidepressants(SSRI/SNRI)
• Clonidine
• Phytoestrogens

71
Endocrine changes with aging (Harman SM,
UpTODate, Mar6, 2007)

• The function of the growth hormone-insulin-like
  growth factor 1 (IGF-1) system, the male
  hypothalamic-pituitary gonadal axis, and the
  portion (zona reicularis) of the adrenal cortex
  that synthesizes Dehydoeqiandrosterone all
  decline with age in most people.
• Increased hormonal secretion may or may not
  compensate for such decreases in tissue
  responsiveness.

72
Eat Less, Live Longer

• Dietary caloric restriction is the most
  reproducible means of extending longevity and
  maintaining health and vitality.
• It has been shown to be relevant to a wide range
  of species, including primates.
• Examination of key markers of the calorically
  restricted phenotype, such as plasma insulin,
  dehydroepiandrosterone sulfate, and body
  temperature, suggest that they may predict
  longevity in humans as well.
• George S. Roth, PhD JAGS 53,2005

73
Caloric restriction and Longevity

• Calorically restricted organisms have better
  protective mechanisms against multiple and varied
  insults. Their oxygen radical protection and DNA
  repair capacities are better.
• Thermodynamic processtemperature
  drop,--metabolic shift.
• In humans (not calorically restricted), lower
  temperature, lower insulin levels, higher DHEAS
  levels a survival advantage.
• George S. Roth, PhD JAGS 53,2005

74
Torch Your Tongue for Weight Loss

• Eating something spicy at the start of your meal
  may help you eat less. A study found that you may
  eat as much as 16 less with a spicy beginning to
  your meal. The researchers believe that the spicy
  food may lead to eating less dense food for the
  rest of the meal.
• Centrum, daily essentials 2006

75
ResveratrolFountain of Youth?

• Present in red wine and in the skin of grapes.
• It is an antioxidant and protects against free
  radicals that are damaging to human
  macromolecules.
• (The yeast model of aging) It affected a gene
  (sir-2) that may mediated the effects of caloric
  restriction and is linked to life span.(Howitz KT
  et al. Nature 2003425)
• Currently there is not yet any evidence that
  resveratrol extends human life span. (Roth G,
  JAGS,2006 53)

76
Genes affecting life span in animals Los Angeles
Times Dec 25,2006

• Sir2 gene appears to play a key role in extending
  life span when animals restrict their
  caloriesdirects formation of a key enzyme that
  senses how much immediate energy body cells have
  to sustain themselves withResveratrol can
  increase the activity of that enzyme.( Guarente
  LP, Sinclair D)

• SOD, methuselah, P66some of the genes are
  involved in the repair of cell damage,
• Several genetic mutations in mice result in
  lower levels of IGF1. Cells from mice with less
  IGF1 can better resist damage from free radicals
  or heavy poisoning. (Miller R)

77
Phytoestrogens

• Both estrogenic and anti-estrogenic action at
  both alpha and beta estrogen receptors (ER)
• Many phytoestrogens tend to be ER-beta selective,
  an action similar to that of some of the
  available pharmacological SERMs

78
Clinical Trials found No Benefit for treating
hot flashes

• Dong quai
• Evening primrose oil
• A Chinese herb mixture
• Vitamin E
• Acupuncture
• Kronenberg F, PhD, and Fugh-Berman A, MD. Ann
  Intern Med. 2002 137805-813

79
Exercise

• The Ultimate Natural Medicine

80
Muscle Power Why you should get stronger.Miriam
Nelson on strength training for older people,
Christine Gorman Time, July 22,2002

• At around age 35, we start to lose about a third
  of a pound of muscle and gain that much body fat
  every year.

81
The Benefits of Exercise

• Reduction in Overall Mortality
• Cardiovascular Benefit
• Reduction in Cancer Risk
• Weight control

• Maintenance of Health for Older Population
• Improvement in Arthritis
• Improvement in Diabetic control
• Prevention in Osteoporosis
• Mental health benefits

82
Religious involvement and U.S. adult mortality

• 9 - year prospective study of a national sample
  of more than 20,000 adults
• Those attending religious services at least
  weekly experienced about a 7 year longer survival
  (14 years for African Americans).
• Hummer R, Rogers R et al. Demography 1999

83
Religion -- Better Physical Health and Medical
Outcomes
84
Psalms 90 12A prayer of Moses the man of God

• Teach us to number our days aright, that we may
  gain a heart of wisdom.

85
Updated Statement on Hormone Therapy 

• the North American Menopause Society
• February 25,2007Ahead of Print issue of
  Menopause
• Director of the North American Menopause Society
  and panel chair Wulf Utian, MD, PhD, of Case
  Western Reserve University in Cleveland, Ohio

86
(NAMS Feb 2007)Agreement was reached on the
following issues

• All women should receive a comprehensive
  assessment before HT, including mammography and
  bone densitometry, according to clinical
  guidelines.
• The primary indication remains the treatment of
  vasomotor symptoms, and systemic estrogen and EPT
  are approved for this indication.
• When estrogen therapy is considered solely for
  vaginal dryness, topical (not systemic) therapy
  should be considered first-line therapy.

87
(NAMS Feb 2007)Agreement was reached on the
following issues

• Data do not currently support EPT use for
  secondary CHD prevention.
• The data show a reduction in CHD in women 50 to
  59 years old who initiate EPT within 10 years of
  menopause, and an increased risk in women who
  initiate after 10 years.
• The attributable risk for CHD remains very low in
  younger postmenopausal women.

88
(NAMS Feb 2007)Agreement was reached on the
following issues

• The risk for VTE is highest within 1 to 2 years
  after initiation of systemic HT, and VTE risk is
  estimated at 11 additional cases for EPT and 2
  additional cases per 10,000 per year for estrogen
  therapy in women 50 to 59 years old.
• Both estrogen and EPT increase stroke risk, with
  8 additional strokes for EPT and 12 additional
  cases per 10,000 per year for estrogen therapy.

89
NAMS Feb 2007)Agreement was reached on the
following issues

• Large randomized trials suggest a reduction of
  diabetes risk with HT, with a 21 to 35 relative
  risk reduction (RRR) for EPT (15 fewer cases per
  10,000 per year) and a 12 RRR (14 fewer cases
  per 10,000 per year) for estrogen therapy.
• Breast cancer risk is slightly increased with EPT
  use beyond 5 years for 4 to 6 additional invasive
  cases per 10,000 per year.

90
NAMS Feb 2007)Agreement was reached on the
following issues

• Estrogen and EPT reduce risk for osteoporotic
  fractures and should be considered an option for
  women at high risk for fractures within 5 to 10
  years.
• Evidence is insufficient to support the use of
  estrogen/EPT for depression.
• Initiating EPT after age 65 years is not
  recommended for the primary prevention of
  dementia or cognitive decline because risk can be
  increased during the ensuing 5 years.

91
NAMS Feb 2007)Agreement was reached on the
following issues

• Lower than standard doses of estrogen/EPT should
  be considered, such as 0.3 mg of oral conjugated
  estrogens or 0.25 to 0.5 µg of poral micronized
  ß-estradiol, but these have not been tested in
  long-term trials.
• The long-term risk-benefit ratio for nonoral
  administration has not been tested.

92
NAMS Feb 2007)Agreement was reached on the
following issues

• Extended use of the lowest effective dose is
  acceptable, provided the benefits of relief
  outweigh the risks in those at high risk for
  osteoporotic fractures and for further prevention
  of bone loss when alternative therapies are not
  available.
• "Bioidentical" hormones should be used with
  caution in absence of regulatory oversight and
  batch-to-batch variation in quality and purity.

93
(NAMS Feb 2007)Agreement was reached on the
following issues

• Women without a uterus should not be prescribed a
  progestogen with estrogen, and progestogen is not
  generally indicated for low-dose estrogen therapy
  administered locally for vaginal atrophy.
• There is insufficient evidence regarding the
  off-label use of long-cycle progestogen (eg,
  every 3 - 6 months for 12 - 14 days) and vaginal
  or intrauterine administration as an alternative
  to EPT.

94
(NAMS2007)The panel could not reach consensus on
the following

• Whether cessation of HT should be abrupt or
  tapered.
• Whether there is a difference in breast cancer
  risk for continuous vs sequential progestogens.

95
NAMS Feb2007 advisory panel recommends

• comprehensive assessment of the risks and
  benefits in women considering HT depression and
  dementia are not indications for use.

• Consensus was not reached on the mode of
  discontinuation of HT or breast cancer risk for
  different progestogen regimens.

96
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97
Eat Your Veggies

• People who overproduce the inflammatory
  16-hydroxy metabolite in her premenopausal life
  are at higher risk of adverse events from HRT
• This metabolic predisposition can be largely
  rectified through regular consumption of
  cruciferous vegetables (broccoli, cabbage, etc).
• 
  
• Michael Zeligs, MD