T. Watson Jernigan, MD MA
Chairman and Professor
Department of Ob/Gyn
Quillen College of Medicine
DO NOT have a financial interest/arrangement or
affiliation with one or more organizations that could be
perceived as a real or apparent conflict of interest in the
context of the subject of this presentation.
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“As a result of participating in this activity,
the participant will be able to…”
…appreciate the impact of the W.H.I. on the
treatment of Menopausal Symptoms
…demonstrate an understanding of
subsequent studies reviewing the use of
hormonal therapy
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…apply the principles of treatment based on
current practice guidelines and position
statements to current patients
…appreciate that the modality of therapy
plays a marked role in the treatment of
current menopausal patients
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This lecture is designed to evaluate the
evolving use of hormones in postmenopausal
patients since the publishing of the W.H.I.
Study. It will discuss the evidence based
medicine that has led this physician in his
prescribing of hormonal therapy. It is hoped
that this journey will impact the prescribing
habits of other providers.
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Use of estrogens can improve menopausal
symptoms such as hot flashes (1940s)
Use of estrogens can cause thromboembolic
phenomenon (1950s)
Use of estrogen can improve subjectively
feminine sense of well being (1960s)
Use of unopposed estrogen can lead to
endometrial hyperplasia or endometrial
cancer (1970s)
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According to records of prescriptions, there
were 129 million prescriptions for Hormonal
Therapy (HT) including estrogen in the year
2000
In 2001, a Women’s Health Initiative (WHI)
study was undertaken to evaluate the efficacy
of Estrogen and Progestin as well as Estrogen
alone in preventing heart disease in
postmenopausal women
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After the 2002 WHI study was published
approximately 65% of women on HT stopped
therapy
In 2003, there were just over 76 million HT
prescriptions dispensed
By 2008, this number had dropped to
approximately 42 million prescriptions for HT
in USA (29 million were for estrogen only RXs)
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“Trends in hormone therapy use before and
after publication of the Women’s Health
Initiative trial: 10 years of follow-up”
Published 2009 but showed the impact of the
W.H.I. on European prescribing of estrogen in
Barcelona, Spain
By 2007, there was a peak reduction of 89%
in percentage of overall prevalence
Barbaglia, Gabriela MD, et al, Menopause Vol. 16, No. 9,
2009; 1061-1064
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This was a retrospective cohort study of
300,000 inhabitants in Barcelona, Spain from
1998-2007
Women ages 50-69 years were evaluated
The age groups evaluated were: 50-54; 5559; 60-64; and 65-69
In addition to prevalence, the percentage of
new users was also evaluated
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Use of estrogen in postmenopausal patients
should not be used in prevention of chronic
illnesses especially cardiovascular disease
Use of estrogen if started should be
considered early in Menopause (ages 50-59)
for benefit of specific symptoms
Use of estrogen in postmenopausal patients
is not for everyone
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“Postmenopausal Hormone Therapy and Risk
of Cardiovascular Disease by Age and Years
Since Menopause”
Rossouw et al reviewed the original data of
the WHI and created a secondary analysis
The study reviewed both arms of the trials (E2
+ P4 and E2 alone)
Rossouw, J. E. et al JAMA 2007; 297: 1465-1477
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In the combined trials, there were 396 cases
of CVD and 327 cases of stroke in the
hormone treated group
In the combined trials, there were 379 cases
of CVD and 239 cases of stroke in the
placebo group
For women with less than 10 years since
Menopause, the RR was 0.76 95% CI 0.501.16
Rossouw, J. E. et al JAMA 2007; 297: 1465-1477
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Rossouw et al stated, “These analyses,
although not definitive, suggest that the
health consequences of hormone therapy
may vary by distance from menopause, with
no apparent increase in CHD risk for women
close to menopause, and particularly high
risks in women who are distant from
menopause and have vasomotor symptoms.”
Rossouw, J. E. et al JAMA 2007; 297: 1465-1477
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Use of Alternative Therapies (e.g. black
cohosh, soy, dong quai) have not been shown
to have “statistically significant” improvement
of VMS in postmenopausal women
Use of estrogen should be started at the
lowest possible dosage
Use of estrogen by topical or non-oral route
should be considered to avoid the First Pass
Effect of the liver
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Reviewing the literature, I have made several
decisions
Lack of estrogen causes hot flashes, night
sweats, and VMS
These VMS can be substantial and in certain
patients cause a change in quality of life
The treatment for VMS is estrogen
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In patients who have undergone
hysterectomy, I discuss the use of estrogen
for severe VMS and other quality of life issues
Given the difficulty with Alternative Therapies
and the First Pass Effect of the Liver, I discuss
extensively non-oral approach to treatment
Use of patch, cream, gel, lotion, and vaginal
ring are legitimate treatments
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If the patient is agreeable, I start with the
lowest dosage possible for four (4) weeks
After 4 weeks, I see the patient in follow-up
to discuss the effectiveness of treatment
It will take upwards of two weeks to see
improvement of the number or the intensity
of the VMS for the patient
If there is excellent control of the VMS, the
patient is seen in three months
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In patients who have severe atrophic vaginitis
and have reservations about use of systemic
estrogen, then I offer topical vaginal estrogen
either by cream or tablet
In some patients who are already on systemic
estrogen for VMS but continue to have
problems with severe atrophic vaginitis, I will
supplement with topical vaginal estrogen
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Once a patient is stabilized on the estrogen
for VMS/Quality of Life issues, she is seen at
6 months and then 12 months
Every year she returns for her annual
examination including pap smear and
mammogram, a discussion regarding the use
of estrogen is done
New information from the literature is given
to the patient and discussion regarding
continuation of therapy commences
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In patients who have not had a hysterectomy
(have an intact uterus), the discussion
regarding therapy is more extensive
The patient is specifically explained about the
WHI and the risk of breast cancer
The severity of the VMS is weighed against
the concerns generated for breast cancer
If patient wishes to proceed, she is started on
estrogen alone first
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The same principles for starting estrogen
(lowest dosage, non-oral) are followed
The patient is continued on increasing
dosages of estrogen until her VMS are
stabilized
Once the VMS are treated, then
progestin/natural progesterone is added to
prevent endometrial stimulation
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In neither scenario do I obtain Serum
Estradiol Levels or for that matter LH/FSH
unless patient is uncertain she is
postmenopausal
I do not do pretreatment endometrial biopsy
or transvaginal ultrasound
I do mandate a pretreatment mammogram
for determining occult breast cancer/ breast
calcifications
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After a patient has been on either estrogen
alone or estrogen with progesterone for
greater than one year, I talk seriously about
decreasing the amount of medication or even
stopping the medication
If VMS recur, then the patient will resume at
her previous treatment dosages
Most patients use the hormonal therapy for
an average of 3-4 years
“OR WHAT DO I REALLY THINK
IS GOING TO HAPPEN”
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RELATIVE RISK
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14
2.2
1.8
1.6
1.3
0.7
◦ 1.3
CHARACTERISTIC
2 FAMILY MEMBERS WITH BREAST CA
1 FAMILY MEMBER WITH BREAST CA
OBESITY
YOUNG AGE AT MENARCHE
>30 AT BIRTH OF FIRST CHILD
MENOPAUSE <49 YEARS OF AGE
HORMONE THERAPY (E+P)<5 YEARS
Archer, David. “Postmenopausal HRT: What is fact, what is
fiction” OBG MANAGEMENT; June 2006: 76-85.