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Menopause Division of Urogynecology and Reconstructive

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Menopause Division of Urogynecology and Reconstructive Pelvic Surgery Department of OB/GYN SERMs Estrogen Raloxifene Tamoxifen Prevent OP ... – PowerPoint PPT presentation

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Title: Menopause Division of Urogynecology and Reconstructive


1
Menopause
  • Division of Urogynecology and Reconstructive
    Pelvic Surgery
  • Department of OB/GYN

2
Epidemiology
  • Average age is 51.4 years
  • 95 confidence interval of Bell Curve gives a
    range of 45-55 years. Less than 2 occur before
    age 40.
  • Factors associated with early menopause
  • Cigarette smoking (1.5 yrs earlier)
  • History of short intermenstrual interval
  • Family history
  • Chemo / Radiation / Genetic factors
  • Unrelated to number of prior ovulations,
    pregnancies, use of OCPs, height, weight, age at
    menarche, race, class or education

3
Elderly Population
  • In 2000, life expectancy
  • Women 79.7 years
  • Men 72.9 years
  • Once you reach 65
  • Women expect to live until 84.3 years old
  • Men expect to live until 80.5 years old
  • Therefore, more than 1/4 of a womans life is
    spent in menopause

4
Peri-menopause
  • Peri-menopause
  • Transitional period
  • Hallmark is menstrual irregularities
  • Shortened cycle length
  • Skipped cycles
  • 10 of women will have abrupt cessation of menses
  • Median length of 4-5 years
  • Median age of onset is 47.5 years

5
Physiology
  • General feature is depletion of follicles with
    loss of granulosa and thecal cell function
  • 6-7 million oocytes at 20 weeks fetal age
  • 1 million oocytes at birth drop to 400,000 at
    puberty
  • 300-400 ovulatory events over lifetime
  • Accelerated follicular loss 2-8 yrs before
    menopause

6
Physiology
  • Granulosa cells produce less inhibin, which
    provides negative feedback for FSH secretion by
    the pituitary gland.
  • Increase in FSH levels
  • After menopause, LH levels are also elevated.
  • Would you check a FSH or LH level to diagnose
    menopause?

7
Symptoms
  • Menstrual irregularities is the primary reason
    women seek medical attention
  • Cycles shorten as increased FSH triggers early
    ovulation
  • Skipped cycles due to anovulation
  • Long periods of anovulation can lead to excessive
    estrogen states and irregular, unexpected menses

8
Symptoms
  • Do you think the perimenopausal women can get
    pregnant?
  • YES
  • Guinness World Record 57 yrs 120 days
  • So, remember to recommend contraception. Low does
    oral contraceptives may be used in women without
    contraindications (i.e. smoking).

9
Symptoms
  • Hot Flushes
  • Subjective feeling of intense heat followed by
    skin flushing and diaphoresis.
  • Sudden dilation of peripheral vasculature
    secondary to abrupt estrogen withdrawal. Skin
    temperature increases and core temperature drops.
  • Usually, occurs for a few seconds to minutes.
  • Duration is about 1-2 years. 25 for gt 5 years.

10
Symptoms
  • Genitourinary atrophy
  • A variety of symptoms
  • Atrophic vaginitis, urethritis, recurrent UTIs,
    dyspareunia
  • Pelvic organ prolapse is NOT caused by estrogen
    deficiency

11
Symptoms
  • Urinary Incontinence
  • Atrophy of estrogen-dependant tissues such as the
    urethra may contribute to existing causes for
    urinary incontinence
  • Typically addressed with local application of
    estrogen cream

12
Symptoms
  • Sexual Disturbances
  • Decreased interest in sexual activity
  • May be related to decreased testosterone levels
  • May be related to psychosocial stressors
  • Anatomic changes secondary to estrogen deficiency
  • Atrophy of vaginal mucosa and lower urethra
  • Thinning of vaginal mucosa with decreased
    lubrication and elasticity, leading to
    dyspareunia

13
Symptoms
  • Sleep Disturbances
  • Estrogen appears related to producing restful,
    deep-stage sleep
  • Hot flushes more common at night
  • Wakening or disruption of deep-stage sleep
  • Contributes to feeling of overall fatigue

14
Symptoms
  • Mood Swings / Irritability / Depression
  • NOT associated with menopausal hormone changes
    alone
  • Stage of life associated with multiple changes
    (e.g., children leaving home, parents aging,
    retirement)
  • Hot flushes and fatigue can lead to emotional
    lability

15
Symptoms
  • Cognitive Function
  • Some types of memory and brain function may be
    influenced by estrogen
  • Some evidence suggests that Alzheimers disease
    is less frequent in estrogen users and the effect
    was greater with increasing dose and duration of
    use.

16
Adverse Health Effects
  • Cardiovascular Disease
  • Leading cause of death in US women (f/b
    malignancies, cerebrovascular disease and MVAs)
  • Death rate for CV disease is 3X the rate for
    breast cancer and lung cancer.
  • Changes in lipid profile in menopause
  • Increased LDL
  • Decreased HDL
  • ? Decrease in triglycerides

17
Adverse Health Effects
  • Osteoporosis
  • Spinal bone density peaks at 20 years, while
    cortical bone density peaks in late 20s
  • Rate of loss of 0.5/year prior to age 40, then
    anywhere from 2-9/year for first 10-15 years
    after menopause
  • Primary loss is trabecular bone, leading to
    compression fractures, loss of height, kyphosis

18
Adverse Health Effects
  • Osteoporosis
  • Osteopenia BMD between -1 and -2.5 SD of a
    young, white adult woman.
  • Osteoporosis BMD -2.5 or greater SD
  • 25-50 of women will have spinal compression
    fractures by age 70
  • 20 of Caucasian women age 80 will have hip
    fractures, with 15-20 mortality.
  • Annual incidence is 1.3 after age 65

19
Adverse Health Effects
  • Osteoporosis
  • High risk
  • Caucasian, Asian
  • Thin, inactive, smokers
  • High caffeine/alcohol intake, low dietary
    calcium, high dietary protein and phosphates
  • H/o oligomenorrhea, excessive exercise, eating
    disorder
  • Medical conditions hyperthyroid, cancer,
    myeloproliferative disorders
  • Low Risk
  • African American
  • Obese, active

20
Adverse Health Effects
  • Osteoporosis
  • Protection
  • Ca supplements (1200mg, 1500mg)
  • Weight-bearing exercise
  • HRT estrogen increases
  • Intestinal calcium absorption
  • Renal conservation of calcium
  • Increases 1,25-dihydroxyvitamin D (active form)
  • Vitamin D (400-800IU)

21
Hormone Replacement
  • Types of hormone replacement
  • Estrogen alone (for women without a uterus)
  • Estrogen and progesterone
  • Sequential
  • Continuous
  • Local estrogen
  • SERMs (Selective Estrogen Receptor Modulators)

22
HRT - Advantages
  • 1. Relief of vasomotor symptoms
  • HRT is effective in reduces the number of hot
    flashes
  • 6-8 weeks to see maximal effect
  • Combination HRT (0.625mg estrogen/2.5mg MPA)
  • What about lower doses of HRT?
  • For combination HRT, all doses resulted in
    similar relief of symptoms
  • For estrogen alone, most relief with higher doses

23
HRT - Advantages
  • 2. Vaginal atrophy
  • Menopause thins the vaginal epithelium and
    increases the vaginal pH (gt 6.0).
  • Estrogen decreases the vaginal pH, thickens the
    vaginal epithelium and reverses vaginal atrophy.
  • Less atrophic changes with higher doses of HRT

24
HRT - Advantages
  • 3. Bone protection
  • Reduction of bone loss
  • Prevents OP-related hip fractures
  • Protects the spine and the small bones
  • WHI 5 fewer hip fractures per 10,000 person-yrs

25
HRT - Advantages
  • 4. Colon cancer
  • Some observational studies have suggested a
    reduced risk.
  • WHI 6 fewer cases / 10,000 person-yrs

26
HRT - Disadvantages
  • 1. Endometrial cancer
  • 8-10 fold increased risk with unopposed estrogen.
  • PEPI unopposed estrogen x 3 yrs 24 with
    atypical hyperplasia (vs 1 women on placebo)
  • Risk is increased with
  • Increased duration and dose
  • Continuous versus cyclic therapy
  • Absence of a progestin

27
HRT - Disadvantages
  • 2. Breast cancer
  • Meta-analysis of 51 case-controlled cohort
    studies showed no increased risk with short-term
    use.
  • After 5 years of use, risk increased by 35.
  • WHI 8 more invasive cases / 10,000 person-yrs
  • Women diagnosed with breast cancer while using
    HRT have been shown to have better survival

28
HRT - Disadvantages
  • 3. Thromboembolic disease
  • Increases risk for DVT 2 3.5 fold
  • Strokes 8 more / 10,000 person-yrs
  • PEs 8 more / 10,000 person-yrs

29
HRT - Disadvantages
  • 4. Cardiovascular disease
  • Traditionally, HRT was thought to provide
    protection against coronary heart disease (CHD)
  • Observational studies found lower rates of CHD in
    postmenopausal women on HRT.
  • The consensus was that CHD was about 35-50 lower
    in women using HRT.
  • Many studies showed that HRT improved lipid
    profiles.

30
HRT - Disadvantages
  • 4. Cardiovascular disease
  • What about secondary prevention? i.e. women who
    have a h/o coronary heart disease, does HRT help?
  • Heart and Estrogen/Progestin Replacement Study
    (HERS) was a RCT, double-blinded study of 2,763
    PM women with intact uteri and a h/o CHD
  • 52 higher rate of major coronary events in the
    1st year
  • Then there was a reduction in the risk with
    longer use i.e. 33 lower risk in the 4th and
    5th years

31
HRT - Disadvantages
  • 4. Cardiovascular disease
  • What about primary prevention? i.e. in healthy
    women, does HRT prevent CHD?
  • Womens Health Initiative (WHI)
  • RCT of 16,608 postmenopausal women aged 50-79
    years old with an intact uterus
  • 40 different US centers
  • Combination HRT 0.625mg CEE and MPA 2.5mg vs
    placebo

32
HRT - Disadvantages
  • 4. Cardiovascular disease (WHI)
  • 7 more CHD events
  • 8 more strokes
  • 8 more PEs
  • 8 more invasive cancers
  • Study stopped after 5.2 yrs (planned 8.5yrs)
    because of cases of breast cancer

33
SERMs
  • Selective estrogen receptor modulators
  • Work as agonists and antagonists depending on the
    tissue
  • Raloxifene and tamoxifen

34
SERMs
  • Estrogen Raloxifene Tamoxifen
  • Prevent OP ? ? ? ? ? ?
  • Risk Breast ? ? ? ? ? ?
  • Cancer
  • Hot Flashes ? ? ? ? ?
  • Endometrial ? ? no effect ?
  • Cancer
  • Venous ? ? ? ? ? ?
  • Thrombosis

35
SERMs
  • Overall, SERMs can help to prevent OP and breast
    cancer
  • However, they aggravate hot flashes, the most
    common indication for estrogen therapy.
  • Also, tamoxifen stimulates the endometrium.

36
Alternative Medicine
  • Limited studies with relatively short duration of
    therapy and follow-up.
  • Soy and isoflavones may be helpful in the
    short-term (lt 2 yrs) for vasomotor sx and may
    protect against osteoporosis.
  • 35-75mg qd isoflavones / day
  • Black cohosh may be helpful in the short-term (lt
    6 mos) for vasomotor symptoms.

37
Summary
  • Health Risks
  • Osteoporosis
  • Lipid abnormalities
  • Cardiovascular disease
  • Cancer

38
Summary
  • Menopause is the natural course aging of the
    female reproductive system, driven by loss of
    oocytes
  • Symptoms of menopause include
  • Menstrual irregularities
  • Hot flushes
  • Sleep disturbances
  • Mood changes
  • Sexual disturbances
  • Urinary incontinence
  • Cognitive function
  • Hair growth

39
Hormone Replacement
40
Abnormal Bleeding
  • A 44-year old woman presents for evaluation of
    abnormal menstrual bleeding. Her periods have
    been regular in the past but for the last 6
    months she has had a period every 35-56 days,
    lasting 7-9 days. The bleeding is heavier than
    usual and she feels tired all the time. She has
    gained 15 lbs over the last 2 years, which she
    believes is due to lack of exercise and increased
    eating/sleeping. She complains that her skin is
    dry. Exam is unremarkable. What would your
    recommend next?
  • Check pregnancy test
  • Discuss exercise / eating patterns
  • Check TSH, PRL
  • Consider endometrial biopsy
  • Expectant management versus hormonal management

41
Health Maintenance
  • 58 year old postmenopausal woman referred to you
    by a friend. She has no known medical problems
    and is on no medications. Her social history is
    remarkable for an 80-pack/year history of tobacco
    use. Her physical exam is unremarkable. What are
    the important health maintenance aspects of the
    exam to focus on?
  • Blood pressure
  • Pelvic exam
  • Breast exam / mammography
  • Fecal occult blood
  • Smoking cessation
  • Flu shot
  • Osteoporosis

42
Abnormal Bleeding
  • A 47 year old woman, G2P2, presents with
    menstrual cycles varying in length from 20 to 40
    days. Until 9 months ago she had regular 28 day
    cycles. She reports frequent hot flushes. She
    recently resumed sexual activity and uses no
    contraception, but she does not desire pregnancy.
    She does not smoke and has no other medical
    problems. Her physical exam is unremarkable. What
    are her options for cycle control?
  • Low dose combination oral contraceptive
  • Continuous low dose estrogen and progestin
    menopause regimen
  • Cyclic progestin therapy for 12 days a month
  • Continuous low dose estrogen (0.625mg conj EE)
  • Estradiol vaginal ring

43
Osteoporosis
  • A menopausal patient with osteoporosis has been
    reading information on the Internet about
    different treatment modalities for osteoporosis.
    She wishes to know more about what therapies are
    actually available and how they work?
  • Estrogen Reduces osteoclast activity
  • SERMs Reduces osteoclast activity
  • Bisphosphonates Reduces osteoclast activity
  • Take on empty stomach, first thing in AM with 8oz
    water and no food for 30 minutes
  • Take sitting up due to esophagitis risk
  • Calcium supplementation within 4 hours
  • Calcium / Vitamin D supplements
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