This study will examine the safety and effectiveness of a synthetic hormone, CDB-2914, for
treating symptoms of menopause. It will compare the effects of estrogen and CDB-2914 with
those of estrogen and progesterone in postmenopausal women. The study will also evaluate
whether CDB-2914 affects adrenal gland function. CDB-2914 is chemically similar to
cortisol, a hormone that is produced by the adrenal glands and regulates the body's response
to stresses, such as infection or injury.
Healthy women volunteers between the ages of 45 and 70 who have not had a menstrual period
for over a year, are not currently taking hormone replacement therapy, do not smoke and have
not had a hysterectomy may be eligible for this study. Candidates will provide a medical
history and have a physical examination, including a breast and pelvic exam. They will also
provide a blood sample, have a mammogram and pap smear, and be instructed in dietary sources
and/or supplements required to be sure they consume at least 1,000 mg. of calcium each day.
Participants will be randomly assigned to take: a) estrogen plus CDB-2914, b) estrogen plus
progesterone, or c) estrogen plus a placebo (look-alike tablet with no active ingredient)
daily by mouth for 6 weeks. During the study period, they will keep a record of any
symptoms, vaginal bleeding, and other medicines they take. They will return to the NIH
Clinical Center weekly for blood tests and to fill out a questionnaire on mood, appetite,
sleep patterns, menopausal symptoms, and other quality of life issues. At the 6-week visit,
- Bring a 24-hour urine collection
- Have a vaginal ultrasound to evaluate the effects of the medication on the thickness of
the endometrium (lining of the uterus)
- Bring all bottles of study medication for a pill count
- Discuss any unusual or troubling symptoms with the study nurse or physician
A final visit will be scheduled 1 to 3 weeks after the 6-week visit, when participants will
turn in their calendar of daily symptoms and return unused progesterone pills.
Doctors recommend hormone replacement therapy to postmenopausal women as treatment for
symptoms of estrogen-deficiency. However, many women do not take hormone replacement
therapy because of side effects. In women with an intact uterus, estrogen must be given
with progesterone to prevent overgrowth of the lining of the uterus. Side effects from
progesterone may cause women to discontinue hormone replacement therapy.
Compounds that are similar to naturally occurring hormones have been synthesized and studied
for their ability to block or simulate the action of sex steroids such as estrogen and
progesterone. The development of this class of compounds, called selective hormone receptor
modulators, may provide new treatments that are targeted to specific organs or tissues. One
example is the selective estrogen receptor modulator raloxifene, which blocks estrogen
action at the uterus, and acts like estrogen at the bone. Raloxifene has been approved for
use in post-menopausal women as a form of hormone replacement therapy and a treatment for
osteoporosis. It provides many of estrogen's benefits without stimulating the uterine
lining and thus may be taken without a progestin.
This study evaluates the selective progesterone receptor modulator CDB-2914, a man-made
hormone. Other progesterone receptor modulators have been shown to block estrogen's
stimulating effect on the uterus in monkeys. If CDB-2914 has this effect in menopausal
women, it may provide a new approach to hormone replacement therapy. In women studied at
the NIH, single doses of CDB-2914 slowed uterine development or induced menses, depending on
when it was given during the menstrual cycle. Like raloxifene, CDB-2914 has the potential
for use in hormone replacement therapy, but to date the effects of its chronic
administration have not been studied. This study aims to evaluate the safety and the
physiologic and endocrine effects of chronic oral administration of CDB-2914 in
postmenopausal women. All study subjects will receive daily oral estrogen and either
CDB-2914, progesterone or a placebo to evaluate whether CDB-2914 blocks or enhances the
usual effects of hormone replacement therapy on the uterine lining, lipid levels, clotting
factors, bone turnover, hot flashes and quality of life. Weekly blood measurements, quality
of life questionnaires, pre- and post-treatment ultrasound examinations of the uterus and a
single biopsy of the uterine lining will be performed on all study subjects to assess these
Participants must be female gender.
Participants age must be 45-70 years inclusive.
Participants FSH must be greater than 20 mlU/mL assay (this is a two-site
immunofluorescent assay, Abbott Labs, post-menopausal range greater than 20).
Participants must have12 month or greater history of amenorrhea.
No current use of any sex steroid hormone replacement therapy (including selective
estrogen receptor modulators) including transdermal, injectable, vaginal and oral
preparations and willingness to abstain from such use during the study.
Participants BMI 19-30.
Participants must have a normal mammogram and pap smear at study entry.
Participants must be able and willing to maintain a minimum daily intake of 1000 mg
calcium from dietary sources and/or supplements for the duration of the study.
Participants must have a normal pro-time and PTT at screening visit.
Participants must be able to read and speak English fluently so as to allow accurate
self-administration of medication, recording of symptoms and unassisted completion of
Participants must be in good health. Chronic medication use, except for glucocorticoid
use or sex hormone replacement therapy, may be acceptable at the discretion of the
principal investigator. Interval use of over-the-counter counter drugs, other than
aspirin or NSAIDs, is acceptable but must be recorded.
Particippants hemoglobin must be greater than 10 g/dL.
Participants must be willing and able to self-administer daily medication, to complete
self-administered questionnaires, to record daily symptoms and to return to the Clinical
Center for weekly follow-up appointments for a minimum of 8 continuous weeks.
Participants with a history of diabetes mellitus type I or II are not eligible.
Participants with a history of malignancy within the past 5 years are not eligible.
Participants must not have a current use (within 90 days of study entry) of drugs that
affect bone turnover and mineral metabolism such as bisphophonates, parathyroid hormone,
hydrochlorothiazide and calcitonin.
Participants with triglyceride level of 500 mg/ml or greater at initial visit are not
Participants must not use cholesterol-lowering medication currently or within 6 weeks of
Participants with tobacco use currently or within 90 days of study entry are not eligible.
Participants with a history of diseases that alter mineral metabolism such as
hyperparathyroidism, chronic renal insufficiency and hemodialysis are not eligible.
Participants requiring ongoing anti-inflammatory medication (e.g., aspirin, NSAIDs)
whether prescribed or over the counter are not eligible.
Participants with current use of anticoagulants (e.g. Warfarin, heparin), anti-platelet
drugs or history of bleeding disorder are not eligible.
Participants must not use OTC herbal or alternative treatments for hot flashes or other
menopausal symptoms, such as DHEA, soy protein supplements, or other phytoestrogens within
two months of study entry, and unwillingness to abstain from these products during the
Participants must not use drugs that affect the frequency of intensity of hot flashes such
as clonidine or SSRI's within 2 months of study entry.
Participants must not have ischemic heart disease (e.g. angina, myocardial infarction or
congestive heart failure).
Participants must not have significant abnormalities in the history, physical or
Participants must not a history of venous thromboembolic events including deep vein
thrombosis (DVT), pulmonary embolism, retinal vein thrombosis.
Participants must not a history of stroke, complicated migraine, documented transient
ischemic attack or uncontrolled hypertension.
Participants must not absence of the uterus (hysterectomy).