MD Professor of Medicine UNSOM Las Vegas In several cross sectional studies Women taking HRT after menopause appeared to have Less CAD Less Fractures Premarin became the best selling drug in ID: 779509
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Slide1
Controversies in HRT
C.R.Kannan
, M.D.
Professor of Medicine
UNSOM, Las Vegas
Slide2In several cross sectional studies…..
Women taking HRT
after
menopause appeared to have
Less CAD
Less Fractures
Premarin
became the best selling drug in
U.S.History
with
FDA
approval
despite little
or no data on
randomized trials
Slide3Women’s Health Initiative (WHI)
1992
2007
HRT
ERT
versus
Placebo
27,500
What are the protective
effects of HRT in
healthy women
with no obvious disease?
First randomised trial
Slide4Summary
Use of Estrogen Plus Progesterone
in
healthy
women for prevention…….
CAD 29%
Stroke 41%VTE 111%Breast ca 26
%
Colo-
Rectal ca 37%
Hip Fracture 34%
Vert fracture 34%
WHI data: the bone protection is
NOT worth
the
risks. Study was terminated before completion
Slide5Summary
Use of Estrogen
alone
in healthy
women for prevention…….
Stroke VTE BUT NOT Breast
ca
Hip
Fracture
Vert
fracture
WHI data: the bone protection is NOT
worth the other risks
Slide6Criticisms
of the
WHI trial
Is this truly a primary prevention trial?
Would the same CV risk be applicable
if started earlier?
What about other routes of administration?
Can these data be applied to patients taking Estrogen only?
Slide7Can these data be applied to patients taking Estrogen (CEE) only?
Anderson et al JAMA 2004
CHD
CVA
VTE
Breast
CA
Hip
Fract
Slight
increase
NSS
39%
33%
23%
Slight
decrease
NSS
39%
Slide8Even though ERT provides
Bone Protection This Rx is not worth the risk
Many women are coming off ERT
Slide9Even though ERT provides
Bone Protection This Rx is not worth the risk
Many women
came off
ERT
Slide10In 2001 WHI stopped the E+P trial
In 2004 WHI stopped then Estrogen only trial
Many women
came off
ERT
WHI changed practice
ERT prescriptions fell by 70% in 07
Short term use for vasomotor
Sx
Transdermal
HT doubled
vs
PO
Slide11Long awaited
KEEPS trial
Healthy women 42-58 years old within 3 years
of final menses at time of
randomisation
Double blind RCT
727 women
Low dose
oral Estrogen
Trans Dermal
Estrogen
Cyclic monthly
Progesterone
Placebo
O-CEE
Premarin
0.45 mg
Trans Dermal
Estrogen
Climara
50 mcg day
Cyclic monthly
Prometrium
200 mg/d x 12 days
Slide12KEEPS
trial Results
Presented in the
North American Menopause Society in October 2012
Relieved vasomotor
symptoms
Neutral effects on BP
Lowered LDL, Increased HDL
and TG
O-CEE
Premarin
0.45 mg
Trans Dermal
Estrogen
Climara
50 mcg day
Neutral effect on
LDL HDL, TG
Increased Insulin sensitivity
Improved Sexual function
Libido, Arousal
Lubrication
And Orgasm
Slide13Long awaited
KEEPS trial Results
Presented in the
North American Menopause Society in October 2012
No significant RISKS
or BENEFITS regarding
Breast cancer Uterine cancer MI or Stroke VTE
Atherosclerosis
progression
O-CEE
Premarin
0.45 mg
Trans Dermal
Estrogen
Climera
50 mcg day
Study not sufficiently powered to determine risks or benefits on clinical events
Slide14Summary
Short term Rx with
lowest dose estrogen is safe ,
relieves vasomotor
sx
and improves QOL
Remains to be seen
if long term HRT is harmful
when started
early.
As it stands, long term HRT is
not indicated for
prevention of disease
(USPSTF Oct 12, 2012)
ERT is contraindicated in….
Hx
of Breast Cancer
Endometrial Cancer
Strong Family
Hx
of above
Established Heart disease
VTE
?Gall bladder disease
Nicotine abuse
Slide15“I want natural
hormones!”
“Prescription estrogens are not
identical to what my body makes!”
“
Bioidentical
hormones are safer than those made by the industry! ”
“I want my estrogens customized
to my body’s needs!”
“ Test my saliva and customize my hormone replacement!
“ I do not want to take a pill made from horse’s urine!!
Slide16What are
Bioidentical Hormones?
Slide17Definition of terms
Bioidentical
Hormones
Hormones identical in
hormone structure to
endogenous hormones
Synthetic
Synthetic hormones
e.g.
premarin
Customized
Compounded
Formulations
Tailor made, customized
To the individual.
Slide18Myth 1
“
Bioidentical
hormones and
Synthetic hormones are polar opposites.”
Slide19Bioidentical
hormones are also synthetic
Synthetic hormones are also
bioidentical
.
Tri est
Bi-est
Chemically Extracting
diosgenin
from
Plants (yams and soy)
17
β
-
estradiol
The prototypical estrogen
most identical to endogenously
produced hormone is synthesized
And available as brand
e.g
Estrace
Slide20Bioidentical
hormones are also synthetic
Synththetic
hormones are also
bioidentical.
Tri
estBi-est
Chemically Extracting
diosgenin
from
Plants (yams and soy
17
β
-
estradiol
In fact, the most
bioidentical
estrogen is branded, prescription-regulated and FDA approved
Origin of this concept of
Bioidentical
hormones?
Slide21Womens
’ Health Initiative 2001
Use of Estrogen Plus Progesterone
in healthy women carries a risk.
CAD 29%
Stroke 41%
VTE 111%Breast ca 2
6
%
Women came off estrogen.
Other “safer” and “natural”
alternatives were sought .
celebrities got into the act
Spawning a whole new industry.
Slide22Prescription
Regulated
Bioidentical
Customized
Compounded
Bioidenticals
Chemical IdentityTo human hormones
Yes
Yes
FDA oversight
Yes No
Published Research
Yes minimal to none
Dose
Reproducibilty
Exact Inexact , inconsistent
Proven efficacy
Yes No RCT
Slide23Myth 2
“I want natural hormones”
Nature
E2
17
β
Estradiol
Most bioactive estrogen
Produced by dominant follicle
E1
Estrone
Second Most bioactive estrogen.
Derived from E2 and Androgens
E3
Estriol
Least bioactive, derived from E2
Slide24How natural are
bioidenticals?
Tri
est
Bi-
est
Compounded hormone
80 %
Estriol
10%
Estrone
10%
Estradiol
Compounded hormone
Estriol
:
Estradiol
8:1 or 9:1
How natural can it be when it has very little of
Estradiol
, the most bioactive estrogen?
Slide25Myth 2
“I want natural hormones”
Truth
So called
Bioidenticals
Contain very little bioactive
Estrogen!
Slide26Myth 3
“Prescription estrogens are not
Bio identical”
Truth
There are at least 23 products
that are FDA tested and
approved with hormones
identical to
Endogenous estrogen
Slide27Oral
Estrace
0.5, 1 and 2 mg
Dermal
Climara 0.025 to 0.1 mg
Vivelle
0.025 to 0.1 mg
Alora
Dermal
Estraderm 0.05 to 0.1 mg
gel
Estragel
0.035
Local
Vaginal cream and ring
17
β
Estradiol
Progesterone
Prometrium
100 to 200 mg
Slide28Myth 4
“
Bioidentical
hormones are safer than those made by the industry ”
Truth
There are no RCT that have proven that the compounded
bioidenticals
are safer.
Slide29Myth 5
“Customized
bioidentcal
hormone therapy provides better results because it is individualized”
Truth
There are only half a dozen variations available. This is hardly sufficient for ‘individualization’
Slide30Myth 6
“Customized
bioidentcal
hormone therapy can be provided by testing saliva for hormones ”
Truth
Salivary testing is not a
relaible
means of assessing the hormonal status.
Slide31Bioidentical
hormone therapy
Represents unchartered waters.
There are alternatives that have been
Tested and provide the best replacement with the most bioactive
Ingredients.