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LOCAL
PHYSICIAN INVOLVED IN THE CLINICAL STUDY OF RALOXIFENE: FDA
Approves Evista®
(Raloxifene) for the Treatment of Osteoporosis
For a copy of the recent press release (pdf
file), please
press here (30 KB).
For a copy of the summary
listed below (pdf file), please
press here (34 KB).
(press
for pdf file information)
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A
Designer Estrogen: EvistaÒ
(Raloxifene)
General Summary
What is a designer estrogen?
Estrogens stimulate various tissues throughout the
body. A designer estrogen is really a substance that stimulates only
specific tissues in the body while blocking other sites.
Picture a designer
estrogen as a key that fits two different locks (receptors) located in
specific areas of the body. Estrogen
is a master key that opens all the locks including the breast (breast problems)
and the uterus (menstrual bleeding). The
designer estrogens, however, are more
selective and open only one kind of lock found in tissues such as bone, liver
and blood vessels. Interestingly,
the designer estrogens sort of get
“jammed” into the other locks (breast and uterus) thereby preventing
estrogens from stimulating these same tissues (anti-estrogen effects: no
menstrual bleeding and no breast problems).
Technical Classification:
Why is Dr. Sweet so interested in this group of medication?
Dr. Sweet been involved in a phase III clinical study
investigating the effects of Evista on the uterus.
He feels the medication has a wonderful potential for the treatment and
prevention of many diseases that that are found in women.
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What is Evista currently prescribed for?
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Evista
is FDA approved for the prevention and treatment of postmenopausal osteoporosis.
Evista has shown to increase bone mineral density at
the lumbar spine and hip by about 2% over 24 months compared to calcium alone
which lost 1% of the bone mass over the two years. In addition, Evista has been
shown to prevent osteoporotic spinal fractures by about 50%.
The FDA approval data was based on 50 studies
conducted in 28 countries with 12,000 women evaluated in the various studies.
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Who would want to take Evista?
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Documented
postmenopausal thinning of the bones (reduced bone density is osteopenia).
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Documented
post-menopausal thinned bones (osteoporosis).
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Unable
to or do not desire to take estrogens
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Women
who do not want to have vaginal bleeding with therapy-
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Women
who are concerned about the theoretical risks of estrogen and breast cancer-
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Women
with breast pain while taking estrogen-
Interestingly,
in a 1995 Gallup survey, women thought breast cancer was the number one killer
of women, responsible for the 40% of all female deaths when it really ranked
ninth and was responsible for only 4% of all female deaths. In this same
nationwide poll, women thought heart disease caused 19% of the deaths while
breast cancer was responsible for 45% of all deaths, the number one killer of
women.
There
is a perception that breast cancer is far more deadly than is actually the case.
This perception should be considered when deciding which medications should be
prescribed for the treatment of diseases.
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What does Evista do to lipid levels?
- Decreased
total cholesterol by about 6%
- Decreased
LDL (bad cholesterol) by about 10%
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Who would not want to take Evista?
Absolute Contraindications
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Pre-menopausal
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History of deep vein
thrombosis or pulmonary embolism while on estrogen
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Hypersensitivity to the
drug Evista
Relative
Contraindications:
1.
History of liver
failure
2.
Severe Hot flashes (6%
above background)
3.
Severe leg cramps (4%
above background)
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Which is better, estrogen or Evista?
Documented
advantages and disadvantages of the medications are as follow:
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Estrogen
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Evista (Raloxifene)
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General Known Advantages
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Probable Advantages
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Decreased heart disease?
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Decreased ovarian cancer?
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Decreased Alzheimer’s disease?
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Decreased colon CA?
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Decreased urinary complaints?
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Decreased gum diseases?
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Drug-Specific Comparative Advantages
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Prevention of hot flashes
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Replaces bone better than Evista
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Increased HDL (good cholesterol) levels
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Shown to prevent fractures
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No vaginal bleeding with no increased risks of endometrial cancer
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No breast discomfort with no increased risks of breast cancer
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Reduction of spinal fractures by 50%
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No elevation in triglycerides (some studies show reduction)
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Decreased incidence of breast cancer by 60-70%
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Disadvantages
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Menstrual bleeding common
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Theoretical risks of breast cancer
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Increased risks of uterine cancer when given alone when a is uterus
present
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Commonly increases triglyceride levels
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Future Applications
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What are the potential significant complications of taking Evista?
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Are there any medications similar to Evista?
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clomiphene
citrate (ClomidÒ,
SeropheneÒ:
ovulatory medications)
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tamoxifen
(NolvadexÒ:
Treatment of and reduction in the recurrence of breast cancer
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toremifene
(FarestonÒ)
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Evista is the next
generation of medications in the SERM group.
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Who is at risk for Osteoporosis?
According to the National Osteoporosis Foundation (NOF), 28 million Americans
have thinning bones (osteopenia) or actual osteoporosis (Stand up to
osteoporosis: Your guide to staying healthy and independent through prevention
and treatment. Washington, DC: National Osteoporosis Foundation; 1997:10.)
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General
Risk factors:
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Family
history of osteoporosis
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Slender
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Caucasian
or Asian
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Early
menopause
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Smoker
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Alcohol
consumption
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Low-calcium
diet
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Sedentary
lifestyle
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Various
medications (corticosteroid, thyroid medications and some anti-seizure
medications)
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Ø
The NOF
recommend bone mineral density (BMD) testing to women under age 65 with one or
more risk factors.
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The NOF
recommend BMD testing to all women 65 and older.
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The NOF
estimates that one in every two Caucasian women will have an osteoporotic
fracture during their lives.
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How does Evista compare to Fosamax, a drug currently used to treat and prevent
osteoporosis?
One of the significant advantages of taking Evista is that there are no dietary
restrictions in taking the medication compared to Fosamax. Fosamax does
nothing to reduce cholesterol levels compared to Evista. The advantages of
using Evista for breast cancer may be significant compared to both estrogen and
Fosamax. A head-to-head (femoral head?) comparison has not been performed.
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Final Comments:
It is ideal to prevent osteoporosis rather than treat it once it has progressed
and is diagnosed. Estrogen is still an excellent therapy for the
prevention and treatment of osteoporosis and has the advantage of improving a
host of other medical ills. The perception is that estrogen causes breast
cancer. Because of this perception and the adverse effects such as uterine
bleeding and breast discomfort, few women actually take estrogen and disease
prevention is not taking place.
The designer estrogens, such as Evista, have opened the door to selective
therapy without the adverse effects of estrogen. These medications not
only prevent postmenopausal osteoporosis but also may decrease the risk of
breast cancer, a perception in progress.
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References of Interest
1.
Arch Intern Med. 1991;151:2026-32.
2.
Cummings SR. et al. the effect of Raloxifene on risk of breast cancer in
postmenopausal women: Results from the MORE Randomized Trial. JAMA
1999;281:2189-97.
3.
Cummings SR, et al. Reduction of vertebral fracture risk in postmenopausal women
with osteoporosis treated with Raloxifene: Results from a 3-year randomized
clinical trial. JAMA 1999;282:637-45.
4.
Delmas PD, et al. Effects of Raloxifene on bone mineral density, serum
cholesterol concentrations and uterine endometrium in postmenopausal women. NEJM
1997;337:1641-7.
5.
JAMA 1999;282:637-45.
6.
J Bone Mineral Res. 1995;10:175-7.
7.
Walsh BW, et al. Effects of Raloxifene on serum lipids and coagulation factors
in healthy postmenopausal women. JAMA 1999;279:1445-51.
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