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