Transcript Menopause and Your Health

Menopause and Your Health
Celia P. Valenzuela, MD
Assistant Professor
Obstetrics and Gynecology
University of Arizona
[email protected]
Educational Objectives
• Understand hormonal and physical
changes that occur with menopause
• Understand risks and benefits associated
with postmenopausal hormone therapy
• Learn about alternative therapies for
treatment of menopausal symptoms
¡Vida! Educational Series - Promoting Good Health
Midlife Event Viewed Negatively
Midlife Event Viewed Negatively
• Negative experiences coincide
• Onset of major illness or disability in self or loved
ones
• Retirement/financial insecurity
• Care needed for aging parents
• Empty nest syndrome
• Physicians
• Majority of healthy/happy patients do not seek help
• Conflicting and lack of data
• Time consuming
What is Menopause?
• 12 months of amenorrhea (no menses)
• Average age 51
• Derived from the Greek words “men” (month)
and “pausis” (cessation)
• Primary ovarian function stops
• Marks the permanent end of fertility
Perimenopause
• Transition
• Change from normal ovulatory cycles to
complete cessation of menses
• Marked by menstrual irregularity
• May begin years prior to menopause
• Onset of menopausal symptoms
The Reproductive Cycle
Perimenopausal Bleeding
• Anovulatory cycles can lead to hyperplasia
• Prolonged, heavy or frequent bleeding should
raise red flag
• Options for controlling bleeding (and protecting
endometrium against hyperplasia)
• Low dose birth control pills
• Cyclic progesterone
• Mirena intrauterine device
• Ablation may also be used to control bleeding
(need EMB first)
Changes in Hormone Patterns
Changes in Hormone Patterns
• Inhibin levels fall
• Produced by granulosa cells
• Decrease may be from declining number of follicles or
reduced quality/capacity of aging follicles Speroff
• Serum FSH levels rise
• Slight increase in estradiol levels
Changes in Hormone Patterns
• Cycle variability increases
• Hormone levels fluctuate
• FSH and estradiol may return to premenopausal
ranges
• After menopause, ovary no longer secretes
estradiol – continues to produce androgens
(under continued stimulation of LH)
• Elevated levels of FSH and LH = evidence of
ovarian failure Speroff
Perimenopause
Low Dose Birth Control Pills vs
Hormone Replacement Therapy
• Postmenopausal hormone (HRT) regimens do
not suppress ovulation
• Oral contraceptive that contains 20 micrograms
estrogen provides effective contraception
• Even lowest dose OCP provides 4x estrogen
dose in standard (HRT)
Menopausal Symptoms
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Hot flashes
Sleep disturbances
Vaginal dryness
Mood changes
Difficulty concentrating
Memory impairment
Bladder irritability/urgency
Changes in balance
Decreased interest in sex, possibly decreased response
to sexual stimulation
Vasomotor Symptoms
• Most often begin in perimenopause
• Sudden onset reddening of the skin
(head/neck/chest), feeling of intense
body heat, profuse perspiration Speroff
• Intervals vary (minutes to hours)
• More frequent and severe at night
• Generally stop spontaneously
w/in few years, may persist
for many years
• 12-15 % of women in 60’s
• 9% of women after age 70 Casper
Other Causes to Consider
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Thyroid disorders
Pheochromocytoma
Leukemia
Cancer
Infection
A Bit of History:
• Estrogen initially prescribed as treatment for
vasomotor symptoms in 1960’s
• Use declined in mid 1970’s secondary to link to
endometrial cancer
• Use increased again in 1980’s when addition of
progestin determined to be protective
• Indications expanded to include prevention of
diseases of aging
Shifren JL, Schiff I. Role of Hormone Therapy in the Management of Menopause.
Obstetrics and Gynecology; 2010: 115, 4: 839-855.
Nurse’s Health Study
• Observational study
• > 70,000 initially healthy postmenopausal
women
• Decrease in coronary events in women
undergoing hormone therapy
• Women aged 35-55 at baseline
Estrogen Benefits
• Oral estrogen lowers:
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LDL
Lipoprotein(a)
Glucose
Insulin
Homocysteine levels
Oxidation of LDL
• Increases
• HDL
Estrogen Benefits
• One HT study of women taking 0.625 or 1.25 mg
of conjugated equine estrogens with 5 mg
medroxyprogesterone daily showed that total
and low density lipoprotein cholesterol were
reduced to nearly the same extent as that of
women treated with 10 mg simvastatin daily.
• HDL was increased to a greater extent than did
simvastatin in this study.Harman
Estrogen Risks
• Estrogen also increases:
• Triglycerides
• Coagulation factors
• C-reactive protein (inflammatory risk factor for CHD)
• Certain progestogens offset some of estrogen’s
benefitsManson
Hormone Therapy - WHI
• Organized by NIH in 1992
• Set of clinical trials
• Primarily a trial of primary prevention of CV
disease
• Randomized, double blind, placebo controlled
• 27,347 postmenopausal women
• 40 US clinical centers
Hormone Therapy - WHI
• Combined estrogen-progestin arm
• 0.625mg conjugated estrogens and 2.5mg
medroxyprogesterone
• Randomized 16,608 women into either tx or placebo
• May 2002, Data and Safety Monitoring Board
recommended discontinuation of this arm
• Statistically significant increase in breast cancer
• Increase in CV events (CHD, stroke, venous TE)
Hormone Therapy - WHI
• Estrogen only arm
• 0.625 mg conjugated estrogens
• Randomized 10,739 women (s/p hyst)
• Feb 2004, NIH canceled study
• Increased risk of stroke similar to combined arm
• No increase or decrease in CHD
• Trend towards increased risk of probable dementia and/or
mild cognitive impairment
• Reduction in hip fractures
• No increase in breast cancer
Hormone Therapy - WHI
• WHI – largest and longest trial of
postmenopausal women using hormone
therapy (5-7 years)
• Based on previous observational studies,
prevention of chronic conditions of aging in
women, including heart disease, was
expected to be demonstrated
• Instead found that hormones were associated
with a greater risk of CHD
Problems with WHI
• Mean age 63
• Fewer patients in the estrogen only arm (decreased
statistical power)
• Women with significant menopausal symptoms were
excluded (to limit drop out rate) – led to fewer women
close to their age at menopause
• Diagnostic bias possibility?
• 40.5 percent of estrogen-progesterone group, 6.8 of placebo
group, unblinded secondary to vaginal bleeding
• Unblinding not a problem in estrogen only arm Speroff
HERS Trial
• Heart and Estrogen/Progestin Replacement Study
• Secondary Prevention of CV disease
• 2763 postmenopausal women with established CHD
were randomized to placebo or continuous E/P
• Mean baseline age 67
• No reduction in the risk of CHD events
Why the Discrepancy?
• Differences in study participant age
• Most observational studies – started taking around time of
menopause.
• WHI – average age 63
• Timing Hypothesis
• HERS and WHI trials failed to show cardioprotection because
these older women already had atherosclerosis
• Suggests that estrogen therapy is bad for atherosclerotic arteries
but prevents atherosclerosis if begun early enoughBarrett-Conner
Harman SM. Estrogen Replacement in Menopausal Women: Recent and Current
Prospective Studies, the WHI and the KEEPS. Gender Medicine; 2006: 3,4: 254-269.
Reanalysis of Data from WHI
• Secondary analysis of data stratified based on
age and time from menopause
• No increased risk seen in women between 50-59 or in
those within 10 years of menopause (underpowered
to reach statistical significance)
• Stroke increased regardless of age and years since
menopause
• Hazard ratios for breast cancer and total cancer
higher in women who initiated hormone therapy soon
after menopause (both regimens)
Shifren JL, Schiff I. Prentice RL, et al. Benefits and risks of Postmenopausal Hormone Therapy When It Is Initiated Soon After
Menopause. American Journal of Epidiomology 2009; 170: 12-23Role of Hormone Therapy in the Management of Menopause.
Obstetrics and Gynecology; 2010: 115, 4: 839-855.
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WHI Coronary-Artery Calcium Study
• Evaluated 1,064 women who were previously enrolled in
the conjugated equine estrogen arm of WHI – age 50-59
at randomization
• Used Cardiac CT to determine the degree of coronaryartery calcium burden
• Atherosclerotic plaques are associated with future CHD risk
• Imaging was conducted at 28 of 40 centers after a mean
of 7.4 years of treatment and 1.3 years after the trial was
completed.
• Coronary artery calcium scores were measured at a central
reading center without knowledge of randomization status
• Overall distribution of coronary-artery calcification scores
were lower among those receiving CEE compared with
placeboManson
Is Transdermal Better?
Transdermal Estrogen
• Oral estrogen has greater effect on liver – first
pass effect
• Absorbed through intestine, then passes
through liver
• Increases liver production of
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Sex steroid binding globulins
Triglycerides
HDL
Clotting factors
• Liver is not normally exposed to such high levels
of estrogen, except during pregnancy
Ongoing Studies –KEEPS
• Kronos Early Estrogen Prevention Study
• Women aged 42 to 58 years
• At least 6 months, no more than 36 months
postmenopausal
• Randomized to oral CEE 0.45, transdermal 17B-estradiol
0.05 mg, or placebo (Micronized progesterone given
orally 12 days/month).
• Primary prevention trial looking at intermediate markers
of CHD
• Intima-media thickness of the carotid artery
• Accruel of coronary artery calcium (Cardiac CT)
• Variety of risk factors including lipids, inflammatory
factors, coagulation indicators
Ongoing Studies – ELITE
• Early versus Late Intervention Trial with Estradiol
• 643 postmenopausal women
• randomized according to years since menopause (<6 or >10)
• To receive either 1 mg oral estradiol or placebo in double blind
fashion
• Ultrasonography used to measure the rate of change in
thickness of the carotid artery
• Cardiac CT to measure coronary artery calcium
What Now?
• For women with moderate to severe vasomotor
symptoms, depending on individual risk, and
patient’s willingness to accept risk, use the
lowest dose of estrogen (with progesterone, if
uterus intact) effective for the shortest amount of
time possible.
How Long?
• Risk of Breast Cancer:
• For estrogen/progesterone therapy, time is limited by
the increased risk of breast cancer that is seen with
more than 3-5 years of use
• For estrogen only, no sign of an increased risk of
breast cancer was seen during an average of 7 years
of treatment
• Risk of Heart Disease/Stroke:
• Most healthy women below age 60 will not have an
increased risk of heart disease with hormone therapy
• In women below age 60, risks of stroke and blood
clots are less than 1/1000 women per year.
Cessation of Hormone Therapy
• Abrupt withdrawal increases return of moderate
to severe symptoms
• Tapering dose of hormones lowers risk of
recurrent symptoms
• Weaning off
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Decrease to lowest dose first
Decrease by one pill per week, or
Skip 1 day, then 2 days, etc
Slower tapering may benefit women with recurrence
Estrogen Preparations
• Premarin – conjugated equine estrogens
• Comprised mostly of estrone sulfate
• 10 estrogens total
• Doses: 1.25 mg, 0.625 mg, 0.45 mg, 0.3 mg
• Cenestin – conjugated estrogens derived from
plant source
• Similar to premarin
• Contains 9 estrogens
• Enjuvia – also conjugated estrogens derived
from plant source
Estrogen Preparations
• Estratab, Menest – esterified estrogens derived
from plant source
• Result in serum estradiol and estrone levels
similar to premarin
• Ogen – naturally derived, purified estrone
sulfate
• Estrace – micronized preparation of estradiol
• Estratest – esterified estrogens and
methyltestosterone
Oral Combination Preparations
• Prempro
• FemHrt
• ethinyl estradiol (potent synthetic estrogen used
primarily in OCPs) with norethindrone acetate
• Doses = 2.5 mcg/0.5 mg and 5 mcg/1 mg)
• Angeliq
• 1 mg estradiol/ 0.5 mg drospirenone
• Activella
• 1 mg estradiol/ 0.5mg norethindrone
Transdermal Estrogen
• Contain 17-beta estradiol
• Doses range from 25 to 100 mcg/day
• 50 mcg/day is equivalent to 0.625 mg of
conjugated estrogen
• Vivelle-dot
• 0.025, 0.0375, 0.05, 0.075, 0.1/day patch
• Menostar – ultra low dose, 14 mcg/day
• addition of progesterone may be two 14 day
cycles/year
Combined Patches
• Combipatch
• 50 mcg/day 17 beta estradiol
• 0.14 or 0.25 mg/day norethindrone acetate
• Climara Pro
• 45 mcg/day 17 beta estradiol
• 0.15 mg/day levonorgestrel
Topical Estradiol Preparations
• Estrasorb (estradiol emulsion)
• 0.05 mg/day estradiol
• EstroGel
• 0.75 mg/day
• Divigel
• 1 mg estradiol/g (apply 0.25g)
• Elestrin
• 0.87 g gel provides 0.52 mg estradiol
• Evamist
• 1.53 mg/spray
Progesterone Preparations
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Prometrium – natural micronized progesterone
Medroxyprogesterone
Drosperinone
Megestrol acetate
Testosterone derivatives (have some weak andronergic
actions)
• Norethindrone
• Norgestrel
• levonorgestrel
• Progestin Therapy alone may also relieve hot flushes
Protecting the Endometrium
• Daily progesterone
• 10-14 days Q month
• Long-cycle
• Q3-6 months
• Insufficient evidence regarding endometrial safety
NAMS
• Progesterone is a large molecule, does not absorb
well through skin
How do you choose?!?!
How do you choose?!?!
• Transdermal may be more convenient, avoids
liver first pass effect
• Combined may be more convenient
• Plant derived: Estrace, Vivelle dot, Climara,
Prometrium, Cenestin
• May need to change route or dose based on
patients symptoms (eg breast tenderness,
bleeding)
How do you choose?!?!
• Cost (Costco pharmacy)
• Premarin - $180 for 100 tablets
• Estrace - $215 for 100 tablets
• Estradiol (gen) – $10 for 100
• Medroxyprogesterone - $10 for 100
• Fem-hrt - $200 for 84 tablets
• Vivelle-dot – $176 for 24
• Estradiol patch – $100 for 12
What dose ?!
Estrogen Equivalents
• 0.625 mg of conjugated estrogens, esterified
estrogens, estrone sulfate
• 1 mg of micronized estradiol
• 0.05 mg of transdermal estradiol
• 5 mcg of ethinyl estradiol
Alterations of
Estrogen Metabolim
• Anticonvulsants increase hepatic clearance of
estrogen
• Estrogen may increase T4 requirements
• Acute alcohol ingestion increases serum
estradiol
• End stage renal disease – higher serum
estradiol levels Martin
Alternative Therapies
• Lifestyle modifications
• Keeping core temperature cool
• Regular exercise, weight loss
• Relaxation therapy/stress management/reflexology
• Isoflavone supplements:
• Soy, red clover, black cohosh
• Acupuncture
• Black cohosh
• may have estrogenic effect on breast – do not use in
breast cancer pt
Alternatives: SSRIs
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Venlafaxine (effexor)
Fluoxetine (prozac)
Sertraline (zoloft)
Citalopram (celexa)
Paroxetine (paxil)
Desvenlafaxine (pristiq)
Escitalopram (lexapro)
Duloxetine (cymbalta)
Non-Hormonal Treatment Strategies for
Vasomotor Symptoms: A Critical Review.
Hall, Elise; Frey, Benicio; Soares, Claudio
Drugs. 71(3):287-304, February 12, 2011.
DOI: 10.2165/11585360-000000000-00000
Table I . Selective serotonin reuptake inhibitors
(SSRIs) and serotonin-norepinephrine reuptake
inhibitors for treatment of vasomotor symptoms
(VMS)AEs = adverse events; BDI = Beck
Depression Inventory; CEE = conjugated equine
estrogen; GCS = Greene Climacteric Scale; HAMD = Hamilton Depression Rating Scale; HRT =
hormone replacement therapy; MADRS =
Montgomery-Asberg Depression Rating Scale; ol
= open-label; OPL = open-label, placebo lead-in;
RAC = randomized, active comparator; RPL =
randomized, placebo-controlled.
Copyright 2011 Adis Data Information BV. Published by Adis International.
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Alternatives: SSRIs
• Venlafaxine (effexor)
• Selectively inhibits both serotonin and NE reuptake
• No benefit seen above 75 mg
• SE = dry mouth, nausea, insomnia, sexual
dysfunction
• Paroxetine (paxil)
• Avoid in women receiving tamoxifen – reduces
formation of active metabolites
Alternatives: Gabapentin
• Gabapentin reduces frequency of hot flashes
• Large study 420 women with breast cancer – 3
groups, randomly assigned, 8 wks
• Placebo – decrease 15% (hot flash score)
• 300 mg/d – decrease 31%
• 900 mg/d – decrease 46% Rapkin
• Other studies have shown similar results
Alternatives: Gabapentin
• Somnolence = common side effect
• Dose of 300 to 600 HS = useful for relieving hot
flashes that awaken patients from sleep
• HS dosing also reduces other side effects Casper
• Other SE = dizziness, disorientation
Alternatives: Clonidine
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Alpha-2 adrenergic agonist
Reduces central noradrenergic activityRapkin
Modest efficacy
May be considered for women with HTN
Weekly patch 0.1 mg/day
• May increase to 0.2 or 0.3 mg/day
• Side effects: dry mouth, dizziness, constipation,
sedation
• Abrupt cessation may cause rebound HTN
Bioidentical Hormones
• “My friend said I should use compounded bioidentical
hormones.”
Compounded
Bioidentical Hormones
• Patients undergo consultation with
pharmacologist
• Have hormone levels checked by serum or
saliva
• Tend to have doses “tailored” based on
hormone testing
• Pharmacologist sends script to health care
provider for signature
Bioidentical Hormones
• Are plant-derived hormones that are biochemically
similar or identical to those produced by the body or
ovaries
• Begin as soy products or wild yams, get converted to
different hormones in the laboratory.
• Some use this term interchangeably between
compounded bioidentical hormones – this is wrong
Compounded Medications
• Compounding is the combining or altering of ingredients
by a pharmacist to produce a drug tailored to an
individual patient’s special medical needs - for example,
by removing a dye or preservative in response to a
patient allergy.
• Drugs that pharmacists compound are not FDA
approved.
• One study done by the FDA found that 30% of
compounded products failed one or more standard
quality tests performed.
Compounded
Bioidentical Hormones
• Risk for over-treating, increasing risks
• Expensive, generally not covered by health
insurances
• Often promoted by individuals outside medical
community
Bioidentical Hormones
• Compounded bioidentical hormones are not FDA
regulated (not tested for purity, potency, efficacy, safety)
• No official labeling, exempt from including the contraindications
and warnings required by the FDA
• Many prescription hormones approved by the FDA
contain bioidentical hormones
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Estrace (vaginal and oral)
Climara
Estraderm
Estragel
Estrasorb
Estring
Femring
Vagifem
Prometrium
Compounded
Bioidentical Hormones
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ACOG
North American Menopause Society (NAMS)
The Endocrine Society
All agree that
• Compounded hormones are not safer
• Issues regarding purity, potency, and quality are a
concern
Saliva Testing?
• NAMS – does not recommend saliva testing to
determine hormone levels
• Endocrine Society – “salivary hormone tests are
inaccurate and should not be considered reliable
measures of hormones in the body”
• ACOG
• No biologically meaningful relationship between
salivary sex steroidal hormone concentrations and
free serum hormone levels
• Salivary hormone levels vary with diet, time of day,
and other variables Pinkerton
Serum Hormone Levels
• Don’t check
• Evidence-based guidelines recommend
individualization of hormone therapy based on
symptoms, not hormone levels
• Lowest effective dose for shortest time possible!
Effect of Estrogen on Vaginal Tissue
• Maintains collagen content – effects thickness
and elasticity
• Maintains mucopolysaccharides and hyaluronic
acid – keep epithelial surfaces moist
• Maintains optimal blood flow
• Keeps epithelium rich in glycogen
• Glycogen = substrate for lactobacilli, which convert
glucose to lactic acid (creating acidic pH)
• Acidic environment protects against vaginal and
urinary tract infections
Without Estrogen
• Vagina loses collagen,
adipose tissue and ability
to retain H20
• Labia and vulva lose
fullness
• Blood vessels narrow and
secretions from
sebaceous glands
decrease
• Vaginal opening may
narrow
• Vaginal length may
shorten
Without Estrogen
Surface epithelium loses
outer fibrous layer,
decreases ratio of
superficial to parabasal
cells.
Vaginal Atrophy
• With loss of glycogen, pH increases (generally > 5)
• Environment less hospitable for lactobacilli
• More susceptible to pathogens from skin and rectum
• Urogenital problems
• Urgency
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Dysuria
Abacterial urethritis
Recurrent UTIs
Urethral caruncles
Most Common Complaints
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Vaginal dryness
Pruritis (itching)
Discharge – yellow, malodorous
Dyspareunia (painful intercourse)
Vaginal bleeding or spotting
Unlike hot flushes, symptoms do not improve
with time
Vaginal Atrophy – Treatment
• Estrogen replacement
• Sytemic and local are effective
• Low vaginal doses usually do not reach serum levels
sufficient to create systemic side effects (endometrial
stimulation) Bachman
• Creams, rings, tablets similarly effective
Vaginal Estrogens
• Premarin
• 0.625 mg/g (conjugated estrogens)
• ½ g vaginally x 2 weeks, then 2x/week
• Estrace
• 100 mcg/g estradiol
• ½ g vaginally x 2 weeks, then 2x/week
• Vagifem
• 25 mcg estradiol
• 10 mcg tablets approved in 2010
Vaginal Estrogens
• Estring
• Silastic ring impregnated with estradiol
• 6-9 mcg estradiol daily x 3 months
• Femring
• 50 – 100 mcg/day
• Suitable for tx of vasomotor and vaginal atrophy
Should you add a progestin?
Should you add a progestin?
• Low doses do not increase serum estrone or
estradiol significantly (studies have
demonstrated levels remain in postmenopausal
range)
• Higher doses raise serum estrogen
concentrations to as high as 500 pg/mL Bachman
• Low doses:
• 0.3 mg of premarin cream 2x/wk (1/2 g)
• 50 mcg of estrace cream 2x/wk (1/2 g)
• 25 mcg of vagifem 2x/wk
• Add a progestin when levels above this are used
What about patients with
Breast Cancer?
• 12 week study on breast cancer patients taking
aromatase inhibitor and vagifem 25mcg
• Suppression of serum estradiol levels achieved were
reversed at 2 wks post starting vagifem
• For patients with severe symptoms, not on
aromatase inhibitor, failed alternatives 
counsel, discuss with her oncologist
Vaginal Atrophy - Alternatives
• Sexual activity
• Improves blood supply
• Preserves elasticity
• Prevents introital narrowing
• Lubricants
• K-Y Jelly
• Astroglide
• K-Y Liquid beads (silicone based)
Vaginal Atrophy - Alternatives
• Replens
• Long-acting moisturizer
• Polcarbophil-based polymer, binds to vaginal
epithelium, releases H20, produces moist film over
vaginal tissue
• May restore normal vagina pH, does not affect
cytology
• K-Y Silk-E
• Feminease
• Contains mineral oil, glycerin, yerba santa
Physical Changes of Menopause
• Weight gain
• Decrease bone mineral density
Physical Changes of Menopause
• Hair changes:
• Thinning of hair on scalp
• Unwanted hair on face
• Skin:
• 30% of skin collagen is lost during the 1st 5 years
following menopause, followed by an average decline
of 2%/menopausal year (statistics similar to bone
loss)
• Skin becomes drier
Sleep Disturbances
• Sleep studies suggest:
• Nocturnal hot flashes more common during 1st 4 h of
sleep
• REM in subsequent 4 h suppresses hot flashes,
arousals and awakenings
• Sleep is affected by anxiety and depression
symptoms
• Primary sleep disorders = common
• Report of 102 women ages 44-56 who reported sleep
disturbances, 53% had sleep apnea, restless leg
syndrome or both Casper
Summary
• Menopause is defined as 12 months without periods
• Symptoms can start up to 10 years prior
• Best Candidates for hormone therapy are women who:
• Are in their 50’s or younger
• Had their last menstrual period within the last 3 years
• Have moderate to severe symptoms
• Use lowest effective doses of hormones, for shortest
duration possible
• Take individualized risk factors into consideration (high
blood pressure, diabetes, smoking, excess weight,
personal or family h/o blood clots)
• Be wary of compounded hormones
Patient Resources
• menopause.org
• North American Menopause Society
• hormone.org/MenopauseMap
• Endocrine Society
• acog.org/For_Patients
• American Congress of Obstetrics and
Gynecology
References
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Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, Ko M, LaCroix
AZ, Margolis KL, Stefanik ML. Postmenopausal Hormone Therapy and Risk of
Cardiovascular Disease by Age and Years since Menopause. JAMA, April 4, 2007.
297 (13): 1465-1426.
Bachman, G; Santen, RJ. Diagnosis and Treatment of vaginal atrophy. UptoDate.
Available at uptodate.com. Referenced 01/27/09.
Stuenkel, CA. Top 10 Menopause Stories of 2008. Menopause Management,
Women’s health trough midlife and beyond. 2009 January/February;18(1):12-19.
Rapkin, AJ. Vasomotor symptoms in menopause: physiologic condition and central
nervous system approaches to treatment. Am J of Obstetrics and Gynecology 2007
Feb: 97-106.
Speroff, L; Fritz, M. Clinical Gynecologic Endocrinology and Infertility. 2005 Lippincott
Williams & Wilkins. Chapters 17 and 18.
Evans, ML; Pritts, E; Vittinghoff, E, et al. Management of postmenopausal hot flushes
with venlafaxine hydrochloride: a randomized, controlled trial. Obstet Gynecol 2005:
105:161
Harman SM. Estrogen Replacement in Menopausal Women: Recent and Current
Prospective Studies, the WHI and the KEEPS. Gender Medicine; 2006: 3,4: 254-269.
References
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Pal L, Manson JE. Editorial: The Women’s Health Initiative: an unforgettable decade.
Menopause: The Journal of The North American Menopause Society. 2012 19;6:597599.
Estrogen and progestogen use in peri- and postmenopausal women: March 2007
position statement of The North American Menopause Society; Menopause: The
Hourna of the North American Menopause Society; 14(2): 168-182.
Manson, JE, Bassuk, SS. Invited Commentary: Hormone Therapy and Risk of
Coronary Heart Disease – Why renew the Focus on the Early Years of Menopause?
American Journal of Epidemiology; 166(5): 511-517.
Hormone Therapy and Heart Disease. ACOG Committee Opinion, No 420, November
2008.
Compounded Bioidentical Hormones. ACOG Committee Opinion, No 32, November
2005.
Hall e, Frey BN, Soares CN. Non-Hormonal Treatment Strategies for Vasomotor
Symptoms, A Critical Review. Drugs 2011: 71 (3): 287-304.
Manson Je, et al. Estrogen Therapy and Coronary-Artery Calcification. The New
England Journal of Medicine 2007 356;25:2591-2602.
Barrett-Connor E. Hormones and Heart Disease in Women: The Timing Hypothesis
(commentary). American Journal of Epidemiology 2007;166: 506-510.
Kaunitz AM. Editorial: Transdermal and Vaginal Estradiol for the Treatment of
Menopausal Symptoms: the Nuts and Bolts. Menopause: The Journal of the North
American Menopause Society. 2012 19;6: 602-603
References
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