Transcript Menopause Basics

Menopause Basics
Physiology, Perimenopause and Menopause
JoAnn V. Pinkerton, MD
Director, Midlife Health Center
Professor of Ob/Gyn
University of Virginia
2007
Menopause Basics
Learning Objectives:
• Describe the hypothalamic-pituitary-ovarian axis
• Differentiate between Perimenopause and Menopause
• Learn physiologic and anatomic changes at menopause
• Describe typical menopausal symptoms
• Perform focused history +physical for menopausal woman
• Interpret selected laboratory tests to evaluate menopause.
• Counsel patients regarding female sexuality and aging
– physical, emotional, and relationship-based issues
What does menopause mean to women?
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Cessation of menstrual periods
End of reproductive capacity
Hormonal changes
Change of life, a life stage
End of prior symptoms
Beginning of new symptoms
Changing emotions
Changing body
Aging process
Disease risks
Medical care needs
Woods et al. Menopause 1999.
Menopause: The Reality
• Clinical diagnosis
• Permanent cessation of menses
following the loss of ovarian activity
• Lack of menses for 12 months
• Mean age in US is 51 (45-55 years)
• Women will spend one-third to one-half
of their lives postmenopausally
Katz VL, Lentz GM, Lobo RA, Gershenson DM. Comprehensive
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STRAW
Menopause
“The anchor point that is defined after
12 months of amenorrhea following
the final menstrual period (FMP),
which reflects a near complete
but natural diminution of ovarian
hormone secretion.”
Soules et al. Menopause 2001.
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CA MS
Natural (spontaneous)
menopause
“Occurs after 12 consecutive
months of amenorrhea, for which
there is no other obvious pathologic
or physiologic cause.”
Utian. Climacteric 1999.
(Average age in Western world is 51 years)
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CA MS
Premature menopause
“Menopause that occurs in
women at or under 40 years old.”
Utian. Climacteric 1999.
Premature ovarian failure
• Hypergonadotropic
amenorrhea ≥ 40 years old
• Associated with many
other health conditions
(eg, autoimmune, toxic, genetic)
• May not be permanent
• Is not the same as
premature menopause
Premature ovarian failure
(continued)
• Ovarian insufficiency leading to
amenorrhea that occurs in women ≥ 40
• Can be transient (eg, from overexercising, eating disorders, high
stress levels
• Can be permanent (eg, from
autoimmune disease or genetic
abnormalities) and equivalent to
premature menopause
STRAW reproductive
aging system
Length
decreases
-2 days
Stages of Reproductive Aging Workshop. Menopause 2001.
“Symptoms” of perimenopause
• Natural, normal changes, not a disease
• Subtle hormonal changes during the 30s
• Symptoms noticeable during the 40s
• Disturbances may be acute or gradual
• Not all midlife symptoms are attributable
to menopause
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CA MS
Induced menopause
“Cessation of menstruation that follows
bilateral oophorectomy (surgical
menopause), iatrogenic ablation of
ovarian function by chemotherapy
or pelvic radiation therapy.”
Utian. Climacteric 1999.
(No perimenopause transition for
these women)
Premature or induced
menopause: complicating factors
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Early loss of fertility
More severe symptoms
Greater risk of osteoporosis and CVD
Possibly complicated by sequelae of
underlying disease
• Little research regarding benefits/risks
of treatment
Hypothalamic-pituitary-ovarian axis
Pituitary
GnRH (+)
LH FSH
Inhibins
Ovary
Hypothalamus
Estradiol
Progesterone
Reproductive aging
• 1-2 million follicles at birth, only
approximately 1,000 by menopause
• Most follicular loss due to atresia,
not ovulation
• Atresia accelerates at around age 37
• Age-related uterine changes also
contribute to decreased fertility
Ovarian function
in perimenopause
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Ovaries begin decreasing in size
Estradiol still dominant estrogen
Number of follicles decreases substantially
Production of inhibin decreases
Remaining follicles respond poorly
to elevated FSH and LH
• Erratic ovulation results in menstrual
cycle irregularity
Decline in fertility
• Fertility wanes starting at about age 37,
before perimenopause signs occur
• By age 45, risk of spontaneous
miscarriage increases to 50%
• Fertility-enhancing techniques available
• Natural pregnancy still possible until
menopause is reached
Physiology: perimenopause
• Estrogen and progesterone levels
fluctuate erratically
• Very high serum estrogen levels
may result
• Gradual decline in testosterone with
age beginning mid-30s
Zumoff et al. J Clin Endocrinol Metab 1995.
Burger et al. J Clin Endocrinol Metab 2000.
Serum hormone levels
at menopause
Circulating estrogens
Ratio of estrogen to androgen
Sex hormone-binding globulin secretion
Peripheral aromatization of DHEA
to estrone
Reversal of E2 to E1 ratio
• No significant change in
testosterone levels
E, FSH, and inihibins prior and following FMP
Burger et al. J Clin Endocrinol Metab 1999.
Health evaluation
at perimenopause
• Determine the primary complaint(s)
• Medical, psychological, and social history
• Family history
• Complete physical examination
• Determine quality of life
• Laboratory tests
– For differential diagnosis of problems
– Screening tests for specific chronic conditions
Routine screens
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Standard blood screens
Periodic serum cholesterol (total, HDL, LDL, TG)
Fasting glucose
Thyroid screen
Annual Pap test
Periodic stool guaiac test, sigmoidoscopy,
colonoscopy
Annual mammogram
Urine screen, when indicated
Sexually transmitted infections, when indicated
Bone density, when needed
Evaluate
need
contraception
Proportion
of Allfor
U.S.
Unintended
Pregnancies
Age: 1994
Proportion of
all US unintendedby
pregnancies
by age: 1994
Unintended
Pregnancies
Unintended pregnancies
Unintendedpregnancies
Pregnancies
Ending
in Abortion
Unintended
ending
in abortion
Percent
100
90
80
70
60
50
40
30
20
10
0
Less
than 15
15-19
20-24
25-29
Age (years)
30-34
35-39
40 and
older
Henshaw. Fam Plann Perspect
1998.
Confirming menopause
• Age, medical/menstrual history, and
symptoms usually sufficient
• Rule out other causes of symptoms
(eg, thyroid disorder)
• Consistently elevated FSH (> 30 mIU/mL)
diagnostic, but rarely necessary except
with nonsurgically induced menopause
• Serum estradiol testing may be of value;
value of salivary levels unproven
Evaluate risk for specific
conditions and diseases
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Vasomotor symptoms/sleep disturbance
Vulvovaginal health
Psychological health
Cardiovascular disease
Diabetes
Osteoporosis
Cancer
Sexual function
Sexually transmitted infections
Urinary incontinence
Alcohol/drug use/abuse
Domestic abuse/violence risk
Assess all women for
alterable risk factors
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Smoking
Poor diet
Obesity
Lack of exercise
Stress
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Habit-forming drugs
Unsafe sex
Excess alcohol
No seat belts
Therapeutic options
• No intervention/treatment
• Lifestyle modification
• Nonprescription remedies
• Complementary and alternative
medicine (CAM) approaches
• Prescription drugs
• Surgical procedures
Write a lifestyle Rx
• Stop smoking
• Have a nutritionally sound diet
• Achieve and maintain healthy weight
• Reduce stress
• Avoid excess alcohol
• Say no to drugs and unsafe sex
• Wear seat belts
• Exercise regularly
Benefits of regular exercise
• Decreases hot flashes
• Improves mood and sleep
• Decreases/maintains weight
• Supports joint/muscle flexibility
• Prevents bone loss
• Decreases risk of many
other diseases
“Improved control of behavioral risk
factors, such as use of tobacco, alcohol,
and other drugs, lack of exercise, and
poor nutrition, could prevent half of
premature deaths, one-third of all cases
of acute disability, and all cases of
chronic disability.”
US Preventive Services Task Force. Guide to Clinical Preventive Service 1989.
Vasomotor symptoms
• One of the hallmarks of perimenopause
• Includes hot flashes and night sweats
• Recurrent, transient episodes of flushing,
perspiration, and intense warmth on upper
body and face
• Skin temperature increases 1-7 ºC,
returns to normal gradually
• Chill often follows
Causes of hot flashes
• Precise cause is unknown
• Estrogen levels alone not predictive
of hot flash frequency or severity
• Other conditions: thyroid disease,
epilepsy, infection, insulinoma,
carcinoid syndromes, leukemia,
pancreatic tumors, autoimmune
disorders, mast-cell disorders
Hot Flushes May Continue
Years After Menopause
Number of Subjects
50
Ages 29 to 82 Years
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35
30
Number of years women report having
hot flushes as estimated by a survey of 501
untreated women who experienced hot flushes
25
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15
10
5
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9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 26 28 29 30 32 36 38 41 44
Years
Mean age of natural menopause was 49.5 years; mean age of surgical menopause was 43.7 years.
Kronenberg F. Ann NY Acad Sci. 1990;592:52-86. Used with permission.
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Causes of hot flashes
(continued)
• Drugs: tamoxifen, raloxifene
• Lifestyle factors: warm ambient air
temperature, higher BMI, cigarette
smoking, less physical activity
Hot Flashes: Demographics,
Lifestyle, Health
• Symptoms vary by race/ethnicity
– More African Americans and Hispanics than
Caucasians affected
– Fewer Chinese than Caucasian affected
• Significant association with
– BMI
– Passive smoke exposure
– History of premenstrual symptoms
– Use of OTC pain medication
– History of comorbidities
– Perceived stress
– Age
Gold EB et al. Am J Epidemiol. 2004;159(12):1189-1199
Alternative Approaches for Vasomotor
Symptoms: Lifestyle Adaptations
Guidelines from NAMS
– Limited effectiveness
• Cooling body core temperature
• Exercise
• Paced respirations (catecholamine control)
• Relaxing activities
– yoga, massage, meditation, paced respiration,
leisurely bath
• Avoid Triggers
– spicy food, hot drinks, caffeine, alcohol
NAMS Position Statement (Treatment of menopause-associated vasomotor symptoms) Menopause. 2004;11:11-33;
Kronenberg F, Fugh-Berman A. Ann Intern Med. 2002;137:805-813
Huntley AL, Ernst E. Menopause. 2003;10:465-76.
Non-Prescription Remedies
Side effects and drug interactions clearly
occur
Lack long-term safety and efficacy data
– Phytoestrogens/isoflavones
• Dietary or supplements (soy-derived)
• Red clover
– Black cohosh
– Vitamin E - not clinically significant
– Studies show no effect compared with placebo
• Dong quai
• Ginseng
• Evening primrose oil
NAMS Position Statement (Treatment of menopause-associated vasomotor symptoms). Menopause. 2004;11:11-33;
Kronenberg F, Fugh-Berman A. Ann Intern Med. 2002;137:805-813; Huntley AL, Ernst E. Menopause. 2003;10:465-76.
Clinical Management
Mild Vasomotor Symptoms
– For mild vasomotor symptoms
• Encourage lifestyle changes
• Non-prescription remedies- tested short term with
little efficacy over placebo but no evidence of harm
– Dietary isoflavones
– Black cohosh
– Vitamin E
Clinical Management
Mod-Severe Vasomotor Symptoms
• Hormone therapy is only FDA approved
treatment
– “gold standard”
• SSRI’s and gabapentin
–have efficacy in early studies
• Progestogens effective
– however large doses required
• Clonidine (oral or transdermal)
Lifestyle Issues in Menopause
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Vasomotor (hot flushes and night sweats)
Low libido/painful intercourse
Weight gain
Memory problems, difficulty concentrating
Mood swings
Insomnia, fatigue
Dizziness, rapid irregular heartbeat
Atrophic vaginitis, bladder irritability
Headaches
Rapkin AJ. Am J Obstet Gynecol. 2007;196(2):97-106.
OCs:
noncontraceptive benefits
• Suppress vasomotor symptoms
• Restore predictable menses
• Decrease dysmenorrhea
• Enhance BMD
• Prevent endometrial and
ovarian malignancies
OCs: when to stop
• FSH testing not reliable in
perimenopausal women or in those
using OCs
• If contraception needed, continuation
to mid-50s reasonable
• Otherwise, consider stopping early 50s
• Low-dose OC has more hormone
than EPT
Depression or Menopause?
Depression
Depressed1,2
Irritable1,2
Anhedonia1,2
Thoughts
of death1,2
Worthlessness1,2
Menopause
Energy2
Concentration2
Sleep2
Weight change1
Libido1
1. Soares CN, Cohen LS. CNS Spectrums. 2001;6:167-174.
2. Joffe H et al. Psychiatr Clin North Am. 2003;26:563-580.
Hot flushes1
Perspiration1
Vaginal dryness1
Sleep disturbances
• 1/3 - 1/2 of US women aged 40-54 report
sleep problems
• Occur mainly in women with nighttime hot flashes
• Most adults require 6-9 hr sleep nightly
• Potential causes: ovarian hormone changes,
advancing age, onset of sleep disorders
(eg, apnea), stress, painful chronic illnesses
(eg, arthritis), other conditions (eg, CVD, allergies),
drugs (eg, thyroid medication)
• Insomnia produces fatigue, irritability, chronic
illness (eg, CVD), mood disorders (eg, depression)
Improve sleep hygiene
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Lower light and noise
Adjust temperature (cool preferred)
Avoid heavy evening meals
Avoid alcohol, caffeine, nicotine
throughout the entire day
Exercise daily, but not close to bedtime
Use bedroom only for sleep and
sexual activities
Have a regular sleep schedule, even
on weekends
Use relaxation techniques
ET effects on sleep
• Decreases frequency of
− Night sweats1-4
− Periods of wakefulness during the night 3,4
• Reduces sleep latency 1,2
• Improves sleep in menopausal women with
insomnia, even in the absence of vasomotor
symptoms4
• Increases the percentage of REM sleep 2,5
• For EPT, use bedtime dosage of progesterone, a
mild soporific, to improve sleep
1Scharf
et al. Clin Ther 1997.
2Schiff et al. Maturitas 1980.
3Erlik
et al. JAMA 1981.
et al. Am J Obstet Gynecol 1998.
5Antonijevic et al. Am J Obstet Gynecol 2000.
4Polo-Kantola
Uterine bleeding changes
during perimenopause
• Strong predictor of perimenopause
• About 90% of women have 4-8 years of cycle
changes before reaching menopause
• No universal definition of “irregular” but unique
to each woman
• Possible changes:
– lighter bleeding (avg blood loss, < 20ml)
– heavier bleeding (avg blood loss, > 40ml)
– bleeding lasting for < 2 days or > 4 days
– cycle length < 7 days or > 28 days
– skipped periods
Bleeding during
postmenopause
• Must be assessed
• Vaginal causes
• Uterine fibroids
• Endometrial or endocervical polyps
• Uterine or cervical malignancy
• EPT
Diagnostic workup for AUB
• Comprehensive history and
pelvic exam
• Blood tests
• Endometrial biopsy
• Vaginal ultrasound
• Additional tests, such as
sonohysterogram or hysteroscopy
Presenting genital symptoms and
physical signs of vaginal atrophy
Symptoms
Dryness
Itching
Burning
Dyspareunia
Burning leukorrhea
Vulvar pruritus
Feeling of pressure
Yellow malodorous discharge
Signs on physical exam
Pale, smooth, or shiny vaginal epithelium
Loss of elasticity or turgor of skin
Sparsity of pubic hair
Dryness of labia
Fusion of labia minora
Introital stenosis
Friable, unrugated epithelium
Pelvic organ prolapse
Rectocele
Vulvar dermatoses
Vulvar lesions
Vulvar patch erythema
Petechiae of epithelium
Bachmann et al. Am Fam Physician 2000.
Physiology of Vulvovaginal
Changes: Structure and
Histology
– Loss of collagen and
adiposity in vulva1
– Clitoral glans loses
protective covering2
– Vaginal surface thinner,
less elastic; more friable2
1Oriba
HA, Maibach HI. Acta Derm Venereol. 1989;69:461-5.
GA, et al. In: Treatment of the Postmenopausal Woman: Basic and Clinical Aspects. 2nd ed. 1999:195-201.
2Bachmann
Non-Rx therapies
for vaginal dryness
• Vaginal moisturizers effective; also produce
low pH to guard against infection
• Vaginal lubricants ease penetration
• Avoid use of petroleum-based products
• Douches may worsen condition;
antihistamines may have drying effect
• Continued sexual activity and/or
stimulation may benefit vaginal health
ET and vulvovaginal atrophy
• Local estrogen appears at least
as effective as systemic ET
• If genital atrophy present without
vasomotor symptoms, nonsystemic
therapy preferred
• Stimulation of endometrium
observed with high doses, some
advise adding progestogen1
1NAMS
Position Statement. Menopause 2004.
Improvement in vaginal
cytology with local CEE
Baseline
Cycle 1
Open-label, single-treatment group, outpatient study
N = 105 women with data valid for efficacy analysis
Treatment significantly increased superficial and intermediary cells
and decreased parabasal cells (P < .05)
Raymundo et al. International Federation of Gynecology and Obstetrics 2000.
Traditional sex response cycle
Plateau
Orgasm
Sexual
excitement
and tension
Arousal
Reduction
Desire
Time
Kaplan. The New Sex Therapy: Active Treatment of Sexual Dysfunctions 1974.
Sexual Response: Male vs Female
Female sexual dysfunction:
definition and classification
International Consensus Development Conference on Female Sexual Dysfunction
I.
Sexual desire disorders
– hypoactive sexual desire disorder
– sexual aversion disorder
II. Sexual arousal disorder
III. Orgasmic disorder
IV. Sexual pain disorders
– dyspareunia
– vaginismus
– noncoital sexual pain disorder
Basson et al. J Urol 2000.
Female sexual dysfunction
• Affects 20% to 50% of women1
• Multidimensional and multicausal
combining biological, psychological,
and interpersonal factors1
• Physically and emotionally distressing,
and socially disruptive1
• Increases with age2
• Must cause distress to be a dysfunction
1Basson
et al. J Urol 2000.
2Goldstein. Int J Impot Res 2000.
Effect of perimenopause on
parameters of sexual functioning
Cross-sectional data reported from longitudinal, population-based
Australian cohort, 45-55 yrs
↓ Sexual responsivity
↓ Sexual frequency
↓ Libido
↑ Vaginal dyspareunia
↑ Partner problems
Dennerstein et al. Obstet Gynecol 2000.
Physician-Patient Communications Concerning
Sexual Problems May Not Be Optimal
If You Wanted to Talk to Your Doctor About a Sexual Problem,
How Concerned Would You Be About the Following?
There Would Be No Medical
Treatment for Your Problem
46
Your Doctor Would Dismiss
Your Concerns and Say
It Was All Just in Your Head
30
51
20
76
71
Very
Concerned
Somewhat
Concerned
Your Doctor Would Be
Uncomfortable Talking About
the Problem Because It Was
Sexual in Nature
46
0
20
23
40
60
68*
80
100
Percentage
*Numbers do not add up because of rounding; n = 500.
Bennett, Petts & Blumenthal. National Survey of American Adults 25 and Older. Washington, DC: March 1999.
Marwick C. JAMA. 1999:281:2173-4. Used with permission.
Sexual history sample questions
• “Are you sexually active?”
• “Are you having any sexual difficulties
or problems at this time?”
• “Have you noted any change in your
sexual interest?”
• “Are you having any difficulty with
vaginal lubrication?”
• “Do you have any concerns about
your sexual health?”
Bachmann et al. Obstet Gynecol 1989.
Model of complete clinical
care
Communication
Tasks
Opening
Engage
Find It
Empathize
Educate
Fix It
Enlist
63
Closing
Biomedical
Tasks
Criteria for Informed
Decision Making
1. Discussion of patient’s role in decision
making
2. Discussion of clinical issue or nature of
decision
3. Discussion of alternatives
4. Discussion of the pros and cons of
alternatives
5. Discussion of uncertainties of decision
6. Assessment of patient understanding
7. Exploration of patient preference