Menopause
Division of Urogynecology and
Reconstructive Pelvic Surgery
Department of OB/GYN
Epidemiology
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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
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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
Elderly Population
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In 2000, life expectancy:
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79.7 years
72.9 years
Once you reach 65:
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Women
Men
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 woman’s life is
spent in menopause
Peri-menopause
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Peri-menopause
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Transitional period
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Hallmark is menstrual irregularities
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Shortened cycle length
– Skipped cycles
– 10% of women will have abrupt cessation of menses
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Median length of 4-5 years
Median age of onset is 47.5 years
Physiology
General feature is depletion of follicles with
loss of granulosa and thecal cell function
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6-7 million oocytes at 20 weeks fetal age
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1 million oocytes at birth drop to 400,000 at puberty
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300-400 ovulatory events over lifetime
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Accelerated follicular loss 2-8 yrs before menopause
Physiology
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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?
Symptoms
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Menstrual irregularities is the primary reason women
seek medical attention
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Cycles shorten as increased FSH triggers early
ovulation
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Skipped cycles due to anovulation
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Long periods of anovulation can lead to excessive
estrogen states and irregular, unexpected menses
Symptoms
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Do you think the perimenopausal women can
get pregnant?
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YES
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Guinness World Record = 57 yrs & 120 days
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So, remember to recommend contraception. Low
does oral contraceptives may be used in women
without contraindications (i.e. smoking).
Symptoms
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Hot Flushes
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Subjective feeling of intense heat followed by skin
flushing and diaphoresis.
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Sudden dilation of peripheral vasculature secondary
to abrupt estrogen withdrawal. Skin temperature
increases and core temperature drops.
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Usually, occurs for a few seconds to minutes.
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Duration is about 1-2 years. 25% for > 5 years.
Symptoms
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Genitourinary atrophy
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A variety of symptoms
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Atrophic vaginitis, urethritis, recurrent UTIs,
dyspareunia
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Pelvic organ prolapse is NOT caused by estrogen
deficiency
Symptoms
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Urinary Incontinence
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Atrophy of estrogen-dependant tissues such as the
urethra may contribute to existing causes for urinary
incontinence
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Typically addressed with local application of
estrogen cream
Symptoms
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Sexual Disturbances
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Decreased interest in sexual activity
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May be related to decreased testosterone levels
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May be related to psychosocial stressors
Anatomic changes secondary to estrogen deficiency
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Atrophy of vaginal mucosa and lower urethra
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Thinning of vaginal mucosa with decreased lubrication and
elasticity, leading to dyspareunia
Symptoms
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Sleep Disturbances
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Estrogen appears related to producing restful, deepstage sleep
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Hot flushes more common at night
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Wakening or disruption of deep-stage sleep
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Contributes to feeling of overall fatigue
Symptoms
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Mood Swings / Irritability / Depression
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NOT associated with menopausal hormone
changes alone
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Stage of life associated with multiple changes (e.g.,
children leaving home, parents aging, retirement)
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Hot flushes and fatigue can lead to emotional lability
Symptoms
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Cognitive Function
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Some types of memory and brain function may be
influenced by estrogen
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Some evidence suggests that Alzheimer’s disease
is less frequent in estrogen users and the effect was
greater with increasing dose and duration of use.
Adverse Health Effects
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Cardiovascular Disease
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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
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Increased LDL
Decreased HDL
? Decrease in triglycerides
Adverse Health Effects
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Osteoporosis
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Spinal bone density peaks at 20 years, while cortical
bone density peaks in late 20s
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Rate of loss of 0.5%/year prior to age 40, then
anywhere from 2-9%/year for first 10-15 years after
menopause
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Primary loss is trabecular bone, leading to
compression fractures, loss of height, kyphosis
Adverse Health Effects
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Osteoporosis
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Osteopenia = BMD between -1 and -2.5 SD of a young, white
adult woman.
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Osteoporosis = BMD -2.5 or greater SD
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25-50% of women will have spinal compression fractures by
age 70
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20% of Caucasian women age 80 will have hip fractures, with
15-20% mortality.
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Annual incidence is 1.3% after age 65
Adverse Health Effects
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Osteoporosis
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High risk:
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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:
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African American
Obese, active
Adverse Health Effects
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Osteoporosis
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Protection:
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Ca supplements (1200mg, 1500mg)
Weight-bearing exercise
HRT: estrogen increases
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Intestinal calcium absorption
– Renal conservation of calcium
– Increases 1,25-dihydroxyvitamin D (active form)
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Vitamin D (400-800IU)
Hormone Replacement
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Types of hormone replacement
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Estrogen alone (for women without a uterus)
Estrogen and progesterone
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Sequential
Continuous
Local estrogen
SERM’s (Selective Estrogen Receptor Modulators)
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
 What
HRT (0.625mg estrogen/2.5mg MPA)
about lower doses of HRT?
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For combination HRT, all doses resulted in similar relief of
symptoms
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For estrogen alone, most relief with higher doses
HRT - Advantages
2. Vaginal atrophy
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Menopause thins the vaginal epithelium and
increases the vaginal pH (> 6.0).
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Estrogen decreases the vaginal pH, thickens the
vaginal epithelium and reverses vaginal atrophy.
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Less atrophic changes with higher doses of HRT
HRT - Advantages
3. Bone protection
 Reduction
 Prevents
 Protects
 WHI:
of bone loss
OP-related hip fractures
the spine and the small bones
5 fewer hip fractures per 10,000 person-yrs
HRT - Advantages
4. Colon cancer
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Some observational studies have suggested a
reduced risk.
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WHI: 6 fewer cases / 10,000 person-yrs
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
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is increased with:
Increased duration and dose
– Continuous versus cyclic therapy
– Absence of a progestin
HRT - Disadvantages
2. Breast cancer
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Meta-analysis of 51 case-controlled & cohort studies
showed no increased risk with short-term use.
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After 5 years of use, risk increased by 35%.
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WHI: 8 more invasive cases / 10,000 person-yrs
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Women diagnosed with breast cancer while using
HRT have been shown to have better survival
HRT - Disadvantages
3. Thromboembolic disease
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Increases risk for DVT 2 – 3.5 fold
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Strokes: 8 more / 10,000 person-yrs
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PEs: 8 more / 10,000 person-yrs
HRT - Disadvantages
4. Cardiovascular disease:
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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.
HRT - Disadvantages
4. Cardiovascular disease:
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What about secondary prevention? i.e. women who
have a h/o coronary heart disease, does HRT help?
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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
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52% higher rate of major coronary events in the 1st
year
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Then there was a reduction in the risk with longer
use – i.e. 33% lower risk in the 4th and 5th years
HRT - Disadvantages
4. Cardiovascular disease:
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What about primary prevention? i.e. in healthy
women, does HRT prevent CHD?
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Women’s Health Initiative (WHI)
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RCT of 16,608 postmenopausal women aged 50-79
years old with an intact uterus
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40 different US centers
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Combination HRT – 0.625mg CEE and MPA 2.5mg
vs placebo
HRT - Disadvantages
4. Cardiovascular disease (WHI):
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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
SERMs
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Selective estrogen receptor modulators
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Work as agonists and antagonists depending
on the tissue
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Raloxifene and tamoxifen
SERMs
Estrogen
Raloxifene
Tamoxifen
Prevent OP
↑↑↑
↑↑
↑
Risk Breast
Cancer
↑↑
↓↓
↓↓
Hot Flashes
↓↓↓
↑
Endometrial
Cancer
↑↑
no effect
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Venous
Thrombosis
↑↑
↑↑
↑↑
↑
SERMs
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Overall, SERMs can help to prevent OP and
breast cancer
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However, they aggravate hot flashes, the most
common indication for estrogen therapy.
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Also, tamoxifen stimulates the endometrium.
Alternative Medicine
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Limited studies with relatively short duration of therapy
and follow-up.
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Soy and isoflavones may be helpful in the short-term (<
2 yrs) for vasomotor sx and may protect against
osteoporosis.
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35-75mg qd isoflavones / day
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Black cohosh may be helpful in the short-term (< 6
mos) for vasomotor symptoms.
Summary
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Health Risks
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Osteoporosis
Lipid abnormalities
Cardiovascular disease
Cancer
Summary
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Menopause is the natural course aging of the female
reproductive system, driven by loss of oocytes
Symptoms of menopause include:
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Menstrual irregularities
Hot flushes
Sleep disturbances
Mood changes
Sexual disturbances
Urinary incontinence
Cognitive function
Hair growth
Hormone Replacement
Benefits
Detriments
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Vasomotor sx
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Endometrial ca
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Vaginal atrophy
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Breast ca
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Osteoporosis
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VTE
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Colon cancer
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CHD
Abnormal Bleeding
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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?
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Check pregnancy test
Discuss exercise / eating patterns
Check TSH, PRL
Consider endometrial biopsy
Expectant management versus hormonal management
Health Maintenance
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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?
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Blood pressure
Pelvic exam
Breast exam / mammography
Fecal occult blood
Smoking cessation
Flu shot
Osteoporosis
Abnormal Bleeding
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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?
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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
Osteoporosis
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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?
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Estrogen: Reduces osteoclast activity
SERMs: Reduces osteoclast activity
Bisphosphonates: Reduces osteoclast activity
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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