Menopause and Your Health

Celia P. Valenzuela, MD
Assistant Professor
Obstetrics and Gynecology
University of Arizona
cpvalenz@email.arizona.edu

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

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 60s
9% of women after age 70 Casper

Other Causes to Consider

Thyroid disorders
Pheochromocytoma
Leukemia
Cancer
Infection

A Bit of History:
Estrogen initially prescribed as treatment for
vasomotor symptoms in 1960s
Use declined in mid 1970s secondary to link to
endometrial cancer
Use increased again in 1980s 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.

Nurses 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:

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 estrogens

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.
.

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

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
patients 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

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

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

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:I 10.2165/11585360-000000000Table
. Selective serotonin reuptake
00000 (SSRIs) and serotonininhibitors
norepinephrine reuptake inhibitors for
treatment of vasomotor symptoms
(VMS)AEs = adverse events; BDI =
Beck Depression Inventory; CEE =
conjugated equine estrogen; GCS =
Greene Climacteric Scale; HAM-D =
Hamilton Depression Rating Scale; HRT
= hormone replacement therapy;
MADRS = Montgomery-Asberg
Depression Rating Scale; ol = openlabel; OPL = open-label, placebo leadin; RAC = randomized, active
comparator; RPL = randomized,
placebo-controlled.

Copyright 2011 Adis Data Information BV. Published by Adis International.

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

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 patients 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

Estrace (vaginal and oral)

Climara
Estraderm
Estragel
Estrasorb
Estring
Femring
Vagifem
Prometrium

Compounded
Bioidentical Hormones

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

Dont 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

Dysuria
Abacterial urethritis
Recurrent UTIs
Urethral caruncles

Most Common Complaints

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)
g vaginally x 2 weeks, then 2x/week

Estrace
100 mcg/g estradiol
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 50s 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

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,
Womens 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

Pal L, Manson JE. Editorial: The Womens 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

Prentice RL, et al. Benefits and risks of Postmenopausal Hormone Therapy When It
Is Initiated Soon After Menopause. American Journal of Epidiomology 2009; 170: 1223.
Shifren JL, Schiff I. Role of Hormone Therapy in the Management of Menopause.
Obstetrics and Gynecology; 2010: 115, 4: 839-855.
Simon JA. Editorial: Vulvovaginal atrophy: new and upcoming approaches.
Menopause: The Journal of the North American Menopause Society 2009; 16, 1: 5-7.
Stearns, V; Beebe, Kl, Iyengar, M; Dube, E. Paroxetine Contolled release I the
treatment of menopausal hot flashes a rendomized control trial. JAMA 2003; 289:
2827.
Casper, RF; Santen, RJ. Menopausal Hot Flashes. UpToDate; available on
uptodate.com; Referenced 06/06/2012.
Pinkerton, JV. Bioidentical Hormones. OBG Management; 2009, Jan; 21(1):43-52
Martin, KA; Barbieri, RL. Preparations for postmenopausal hormone therapy.
UpToDate; available on uptodate.com; referenced 01/04/09
Menopause Practice, a Clinicians Guide, 4th Edition. The North American Menopause
Society. 2010. Mayfield Heights, Ohio.

References

Santoro, N. Symptoms of Menopause. Clinical Obstetrics and Gynecology;51(3): 539548.

Kalay, AE; Demir, B; Haberal, A; Kalay, M; Kandermir, O. Efficacy of citalpram on
climacteric symptoms. Menopause: The Hourna of the North American Menopause
Society; 14(2): 223-229.
Freedman, RR. Menopause Sleep Disturbance. Menopause Management Womens
Health Through Midlife & Beyond. 2009 Jan/Feb (18(1): 9-11.