Transcript Managing Menopause - Linda Baier Files

Menopause
VETERANS HEALTH ADMINISTRATION
Objectives
Define menopause and perimenopause
Appropriately assess women presenting with
menopause-like symptoms
Review common symptoms and discuss
management options
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Case Study 1
A 45-year-old woman Veteran
presents at your clinic
complaining of severe and
frequent hot flushes. She’s
also noticed several months
of irregular menstrual cycles.
She wonders if she is in
menopause.
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Initial Assessment
Make sure it is
not…
Identify
Triggers
• Cardio-Pulmonary
• Infection
• Hypoglycemia
• Med reaction
• Thyroid
VETERANS HEALTH ADMINISTRATION
• Determine
impact on
the Veteran
- Physical
- Emotional
- Psychosocial
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Premature
Menopause
• Loss of menstrual cycles before age 40
Perimenopause
• Transition from regular ovulatory cycles
toward permanent infertility
• Begins at different ages, even in the 30’s. May
last for years. Includes 1 year after last cycle.
Menopause
Menopause
• Permanent cessation of menstruation resulting
from loss of ovarian function
• No menses for >12 months in women over 45
• Average age is 51
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Menstrual Changes in Peri-Menopause
“Normal” menstrual flow
Menstrual changes
• 21-35 days apart
• Experienced by 90% of women
• Occur 4-8 yrs before menopause
• Flow ranges from very scant to
• Duration: 3-7 days
− Avg 2.4 tbsp of fluid
− Normal range 1-6 tbsp
• Contains blood, cervical
mucus, vaginal secretions,
endometrial tissue
• Reddish-brown, slightly
darker than venous blood
very heavy, bright red bleeding
•
•
Duration: 1 day to 10-12 days
•
Cycles are often anovulatory
Cycle length/frequency: may
stretch to every 60-90 days or
shorten to every 20 days
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Pregnancy is still possible…
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Peri-Menopausal and
Menopausal Symptoms
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Vasomotor Symptoms
• Experienced by 50% to 82% of women
• Duration of 4 to 10.2 years
– 15% report severe flushes for >15 years
• Feelings of intense heat for 30 seconds to 10 minutes
• Greatest frequency is 2-4 years after menopause
• Risk factors:
–
–
–
–
Smoking
Physical inactivity
Obesity
Race (most common in African-American woman, least common
in women of Japanese/Chinese descent)
– Surgical menopause
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Urogenital Atrophy
Physical exam changes
• Loss of labial/vulvar fullness
• Pale epithelium with less folds
• Decreased vaginal secretions
• pH >4.5
Vaginal dryness, irritation, +/- discharge
Dyspareunia (painful intercourse)
Urinary sx (frequency, dysuria, incontinence)
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Other Menopausal Symptoms
Mood
Swings
Loss of Libido
Poor
Concentration
Anxiety
Irritability
Feelings of
dread
Depression
Memory
Lapses
Headache
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Insomnia
Hair
Changes
Managing Vasomotor Symptoms
with Hormone Therapy
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1960. Estrogen is
Fountain of Youth!
1970s. Poison! (linked
to endometrial Ca)
1980s: Good!
(prevents osteoporosis)
1990. Use expands!
(protects heart)
2002. Poison!
(WHI study)
2014 ?
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Hormone Therapy (HT)
• Estrogen therapy seemed logical based on the
hypothesis that menopause:
- Decreased estrogen
- Accelerated cardiovascular disease
Thus… giving estrogen will protect the heart
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Women’s Health Initiative (WHI)
• Prospective study of estrogen + progesterone
(Prempro) or estrogen alone on risks for CHD, breast
cancer, hip fracture
─ E+P for women with intact uterus
─ E alone for women without
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WHI Results
E+P vs.
placebo
Hazard
ratio
E only vs.
placebo
Hazard
ratio
CHD
164 vs. 122
1.29
177 vs. 199
0.91
Stroke
127 vs. 85
1.41
158 vs. 118
1.39
DVT/PE
151 vs. 67
2.13
101 vs. 78
1.33
Breast cancer
166 vs. 124
1.26
94 vs. 124
0.77
Colon cancer
45 vs. 67
0.63
61 vs. 58
1.08
Hip fracture
44 vs. 62
0.66
38 vs. 64
0.61
231 vs. 218
.98
291 vs. 289
1.04
Death
Rossouw et al. JAMA, 2002; Anderson et al. JAMA, 2004.
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WHI Findings
• CHD, DVT/PE, and breast cancer risk all increased
with E+P
• DVT/PE risk increased in both groups
• Similar increased risk of stroke for E+P and
estrogen alone
• No beneficial effect of HT on cognitive function in
older post-menopausal women when
administered for up to 5 years
Rossouw et al. JAMA, 2002; Anderson et al. JAMA, 2004.
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Further Analyses of WHI Data
• Both arms re-analyzed to look for trends in the effect of
HT on CHD, stratified by age and years since menopause
• Women who initiated HT closer to menopause tended to
have reduced CHD risk vs. the increase in CHD risk seen
in women more distant from menopause
– This trend not statistically significant
Rossouw et al. JAMA, 2007.
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Timing of HT and CHD
• Majority of women in the WHI had been menopausal
for at least a decade
- These older women likely had more extensive subclinical
atherosclerosis
• Hypothesis: prothrombotic and proinflammatory
effects of estrogens manifest primarily in women with
subclinical lesions
- Conversely, women with less arterial damage who start HT
early in menopause may derive cardiovascular benefits
Rossouw et al. JAMA, 2007.
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Additional Studies
• Kronos Early Estrogen Prevention Study (KEEPS)
- No beneficial or harmful effect on atherosclerosis progression
with HT vs. placebo after 4.8 years
• BMJ TRIAL
- After 10 years of follow up, women receiving HT early after
menopause had a reduced risk of mortality without any
apparent increase in breast cancer or stroke
• Both studies provide more reassurance about the safety of
HT on the heart if started early in menopause (still not for
appropriate for primary prevention of heart disease)
KEEPS Report, NAMS Annual Meeting, 2012; Schierbeck et al. BMJ, 2012.
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Extended Follow-up of WHI Data
• Neither regimen significantly affected all-cause mortality
during or after the intervention phase
– CEE-alone group: Subset of women aged 50 to 59 had fewer MI
and significantly lower all-cause mortality
– Combination HT has a harmful effect on CHD risk among older
women, results in younger women are inconclusive
• Risk–benefit ratio of HT is most favorable when
initiated in younger menopausal women
– Most risks and benefits from hormone therapy
dissipate after stopping
Manson JE, et al. JAMA,2013
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Breast Cancer Risk with HT
• Per WHI, risk for breast cancer is higher with E+P when
used longer than 5 years; no risk for estrogen alone
• Multiple follow-up studies support “gap” hypothesis:
breast cancer risk increases when HT is started shortly
after menopause vs. after several years delay
• So, timing for breast cancer risk is direct opposition to
HT and CAD
Chlebowski et al. JAMA, 2003; NAMS position statement. Menopause, 2012;
Beral et al. J Natl Cancer Inst, 2011.
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HT and Shared Decision-Making
• Ultimately, it comes down to risks/benefits:
- Most women who want HT will want it within 5 years
- With E + P <5 years, absolute cancer risk is very low (lower
than 1 alcoholic drink/day)
- Many more women will die of CAD rather than breast cancer
- If woman is of average cancer risk with significantly
impairing hot flushes, recommend HT initiation when
symptom control is needed most (early!)
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Current Indications for Hormone Therapy
• Moderate to severe vasomotor symptoms related to
menopause in healthy women
• Patient request/quality of life issues
• Not for chronic disease prevention
• Do not start HT if >10 years after menopause
• Systemic hormones for short-term use only (<5 years)
Individualized decision should be based on risks for CVD,
breast cancer, and osteoporosis as well as quality of life issues
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Hormone Therapy Initiation
• All routes of systemic therapy are equally effective
- Transdermal estrogen has lower risk of VTE vs. oral route
• Use lowest effective dose
- CEE 0.625 mg per day oral (estradiol 50 mcg) or lower
• For women with a uterus, add progesterone
- 2.5 mg of MPA per day
• Continuous regimen is associated with fewer hot flushes
- Women on this regimen are typically amenorrheic
NAMS position statement. Menopause, 2012; Laliberte et al. Menopause, 2011.
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Hormone Therapy Discontinuation
• No optimal approach for immediate cessation vs. taper
• Try prolonged 6-12 month taper if symptoms recur
after an abrupt stop
• North American Menopause Society suggests that
extended use of HT is reasonable for women who feel
that benefits of symptom relief outweigh the risks
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Compounded Bioidentical Hormones
• Typically custom-compounded formulations similar in chemical
composition to those made endogenously
• May combine several hormones and use non-standard routes
of administration
- Estradiol, estrone, and estriol
- Often utilize salivary testing — inaccurate and unreliable
• No rigorous randomized controlled trials to test safety or
efficacy; under-dosage and over-dosage possible because of
variable bioavailability and bioactivity
• No more effective than traditional HT with similar risks/side
effects; inform patients in same manner as FDA-approved HT
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Alternatives to
Estrogen for
Hot Flushes
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Decrease in hot
flush score
Medications
Venlafaxine (Effexor): antidepressant 37.5 - 150 mg
27-61%
Desvenlafaxine (Pristiq): antidepressant 100 & 150mg
60-65%
Fluoxetine (Prozac): antidepressant 20 mg
40-50%
Paroxetine (Paxil): antidepressant 10 - 25 mg
FDA-approved to treat menopausal hot flushes
38-62%
Escitalopram (Lexapro): antidepressant 10 - 20 mg
47%
Citalopram (Celexa): antidepressant 10 - 30 mg
23-55%
Gabapentin (Neurontin): anti-seizure, 300 - 2400 mg
45-65%
ACOG practice bulletin no. 141. Obstet Gynecol 2014; Casper et al. UpToDate, 02/14/11, lit
review through 03/14.
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Vitamin and Herbal Remedies
Vitamin E
No effect
Black cohosh (can harm the liver)
No effect
Evening primrose oil
No effect
Ginseng (may help with mood, insomnia)
No effect
Wild yam (“natural progesterone”)
No effect
Phytoestrogens: isoflavones (soy, red clover)
No effect
Phytoestrogens: lignans (crushed flaxseed)
No effect
Chasteberry
No effect
Dong quai (bleeding problems with blood thinners)
No effect
Licorice root
No effect
Kava (may ease anxiety, can damage the liver)
No effect
*Note: Many herbs are estrogenic and the risks are unclear
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Mind-Body Therapies
Treatment
Efficacy
Paced respiration
Mixed results
Acupuncture
Mixed results
Yoga
Possibly effective?
Exercise
Negative effect on
flushes. Positive
effect on sleep.
Stress management No effect
Relaxation therapy
No effect
Homeopathy/
magnet therapy
No effect
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Comment
Small pilots, 1 randomized
controlled trial
Raises core body temp,
thus triggering flushes
Lifestyle Changes
• Identify triggers and avoid them if possible
– Spicy foods, alcohol, caffeine, chocolate, stress, hot places
•
•
•
•
•
•
Dress in layers and remove the top layer as necessary
Sip a cold drink when flushes occur
Adjust room temperatures
Use fans at home or in the workplace
Consider losing weight to decrease flush frequency
Don’t smoke
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Smoking and Menopause
• Women who smoke >10 cigarettes per day are 40% more likely to
go into menopause earlier than nonsmokers
– Early menopause → heart disease, stroke, osteoporosis
• Smokers have more severe hot flushes and sleeping difficulties
• Women who smoke are 35% more likely to break a hip after
menopause than nonsmokers
– Former smokers have a 15% greater risk of hip fracture
Employ motivational interviewing:
 Is it ok if I give you information about how smoking affects you during
menopause?
 What are some reasons why you might think about quitting?
 What are some things that you can do to cut down on your smoking?
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Summary: Hot Flush Management
• Systemic HT is most effective approach for treating moderatesevere vasomotor symptoms
• Risks for combined systemic HT = thromboembolic disease, breast
cancer
– Non-oral approach safer (no RCT evidence)
• Use lowest effective dose in continuous regimen; re-evaluate
annually
– Estrogen + progesterone for women with a uterus
• Consider non-hormonal alternatives
– Venlafaxine, gabapentin, paroxetine
– Encourage smoking cessation, weight loss
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Managing
Vaginal & Urinary
Symptoms
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Common Symptoms
Vaginal
Dryness
Pruritus
Dyspareunia
+/- Thin watery
discharge
Dysuria
(painful
urination)
Urinary
urgency or
incontinence
Frequent
urinary tract
infections
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Sexual Function and Menopausal Symptoms
• 75% of middle-aged American women consider sexual activity to
be of moderate to extreme importance
• Common menopausal symptoms are associated with diminished
libido: depressive symptoms (P = .003), poor sleep (P = .02), and
night sweats (P = .04)
• Large cohort studies report:
- Prevalence of vaginal dryness… 27% - 55% of women
- Prevalence of dyspareunia… 32% - 41%
Cain et al. J Sex Res, 2003; Reed et al. Am J Obstet Gynecol, 2007; SOGC clinical practice
guidelines no. 145. Int J Gynecol Obstet, 2005.
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Vaginal Atrophy
• Clinical Diagnosis
– Appearance of external genitalia and vaginal mucosa
• Loss of labial/vulvar fullness
• Pallor of urethral/vaginal epithelium
• Decreased vaginal secretions
– pH >4.5
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Vaginal Atrophy Management
Treatment
Pros
Lubricants
OTC • Eases pain during
• Astroglide
intercourse
• K-Y Jelly
• Olive oil
Moisturizers
OTC • Eases symptoms
• Replens (on VA
• Improves vaginal
formulary)
epithelium
• Vagisil
Vaginal estrogen Rx
• Eases symptoms
• Premarin cream
• Improves vaginal
• Estring
epithelium
• Vagifem
• No systemic effects
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Cons
Doesn’t change
vaginal tissue
Expensive option
Not for women
with breast
cancer?
Vaginal Atrophy: Systemic Estrogen
• Systemic estrogen is not recommended for vaginal
symptoms
• Disadvantages
─ Need to add progesterone to protect the uterus
─ Increase in sex hormone binding globulin (SHBG) can
decrease free testosterone
• Transdermal estrogen may have less of an effect
Why incur systemic risks for a local problem?
NAMS position statement. Menopause, 2012.
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Vaginal Atrophy: Local Estrogen
Advantages
• Relieves atrophy and may improve sexual function
• Low dose is effective and all preparations equally effective
• Progesterone generally not indicated when low-dose vaginal
estrogen is administered. Endometrial safety data not available
for use longer than 1 year.
• Can simultaneously treat urinary incontinence
Disadvantages
• May not be appropriate for women with hx of breast cancer
NAMS position statement. Menopause, 2013; Suckling et al. Cochrane Rev, 2006 Oct 18.
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Vaginal Estrogen Comparison
Cream
Ring*
*Non-formulary
Tablet*
Dose
0.5-2gm dose
5-10 mcg daily
10 mcg
Frequency
Nightly for 2 wks
then twice/wk
Replace every 3
months
Nightly for 2 wks,
then twice/wk
Safety
No reports of
endometrial CA
No endometrial
No reports of
proliferation at 1 year endometrial CA
Comments
Can achieve
systemic
estrogen levels
No rise in serum
estrogen
No systemic or
endometrial
absorption
Note: Estring provides local effects only; Femring achieves systemic
levels, which requires adding progesterone to protect the uterus.
NAMS, ©2012. http://www.menopause.org/htcharts.pdf
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Summary: Vaginal Atrophy Management
• First-line therapies include nonhormonal lubricants with
intercourse and, if indicated, regular use of long-acting vaginal
moisturizers
• Estrogen therapy is advised for moderate-severe atrophic vaginal
symptoms or if no response to lubricants and moisturizers
• Ospemifene is another option for dyspareunia
– SERM targeting vaginal tissues
• Spotting or bleeding in a postmenopausal woman with an intact
uterus requires a thorough evaluation
ACOG practice bulletin no. 141. Obstet Gynecol, 2014; NAMS 2012, 2013.
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Urinary Incontinence and Estrogen
• Prevalence during menopausal transition is 8% - 56%
• Urinary incontinence may improve with use of local
estrogen therapy
- No evidence whether benefits continue after stopping
treatment
- No information on long-term effects
• Randomized trials show oral estrogen worsens
incontinence
Cody et al. Cochrane Database Syst Rev 2012 Oct 17.
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Urinary Tract Infections & Estrogen
• Oral estrogens do not reduce UTIs compared to placebo
• In 2 studies, vaginal estrogens reduced the number of UTIs in
postmenopausal women with recurrent UTI
• Intravaginal estrogen may be reasonable for postmenopausal
women with 3+ recurrent UTIs/year, especially when resistance
to multiple drugs limits efficacy of antimicrobial prophylaxis
Perotta et al. Cochrane Database Syst Rev, 2008 Apr 16; Stamm WE. J Infect Dis, 2007.
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Summary
• Menopause symptom management should be based
on an in-depth conversation between patient and
provider
• Critical to identify patient’s biggest concern
• Tailor treatment based on impact of symptoms on
daily life, taking into consideration patient’s
cardiovascular and cancer risk factors
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Resources
North American Menopause Society. Information on menopause
and educational materials.
http://www.menopause.org/edumaterials.aspx
PubMed Health. Fact sheet: menopause.
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004974/
U.S. DHHS. Menopause and menopause treatments fact sheet.
http://www.womenshealth.gov/publications/our-publications/factsheet/menopause-treatment.cfm
U.S. DHHS. Menopause symptom relief and treatments.
http://www.womenshealth.gov/menopause/symptom-relieftreatment/
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Resources
NHLBI. Facts about menopausal hormone therapy.
http://www.nhlbi.nih.gov/health/women/pht_facts.pdf
NIA. Hormones and menopause: tips from National Institute on
Aging.
http://www.nia.nih.gov/sites/default/files/TipSheet_HormonesAnd
Menopause_0.pdf
NCI. Fact sheet: Menopausal hormone therapy and cancer.
http://www.cancer.gov/cancertopics/factsheet/Risk/menopausalhormones
National Center for Complimentary and Alternative Medicine. Herbs
at a glance. http://nccam.nih.gov/health/herbsataglance.htm
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Author
Rachel Bonnema, MD, MS
Nebraska Western Iowa VA Health Care System
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