 |
|
JAMA-EXPRESS
Noncardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy
Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II)
Stephen Hulley, MD, MPH;
Curt Furberg, MD, PhD;
Elizabeth Barrett-Connor, MD;
Jane Cauley, PhD;
Deborah Grady, MD, MPH;
William Haskell, PhD;
Robert Knopp, MD;
Maureen Lowery, MD;
Suzanne Satterfield, MD;
Helmut Schrott, MD;
Eric Vittinghoff, PhD;
Donald Hunninghake, MD;
for the HERS Research Group
JAMA. 2002;288:58-64.
ABSTRACT
| |
Context The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized
trial of estrogen plus progestin therapy after menopause.
Objective To examine the effect of long-term postmenopausal hormone therapy on
common noncardiovascular disease outcomes.
Design and Setting Randomized, blinded, placebo-controlled trial of 4.1 years' duration
(HERS) and subsequent open-label observational follow-up for 2.7 years (HERS
II), carried out between 1993 and 2000 in outpatient and community settings
at 20 US clinical centers.
Participants A total of 2763 postmenopausal women with coronary disease and average
age of 67 years at enrollment in HERS; 2321 women (93% of those surviving)
consented to follow-up in HERS II.
Intervention Participants were randomly assigned to receive 0.625 mg/d of conjugated
estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 1380) or placebo
(n = 1383) during HERS; open-label hormone therapy was prescribed at personal
physicians' discretion during HERS II. The proportions with at least 80% adherence
to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group
and increased from 0% (year 1) to 8% (year 6) in the placebo group.
Main Outcome Measures Thromboembolic events, biliary tract surgery, cancer, fracture, and
total mortality.
Results Comparing women assigned to hormone therapy with those assigned to placebo,
the unadjusted intention-to-treat relative hazard (RH) for venous thromboembolism
declined from 2.66 (95% confidence interval [CI], 1.41-5.04) during HERS to
1.40 (95% CI, 0.64-3.05) during HERS II (P for time
trend = .08); it was 2.08 overall for the 6.8 years (95% CI, 1.28-3.40), and
3 of the 73 women with thromboembolism died within 30 days due to pulmonary
embolism. The overall RH for biliary tract surgery was 1.48 (95% CI, 1.12-1.95);
for any cancer, 1.19 (95% CI, 0.95-1.50); and for any fracture, 1.04 (95%
CI, 0.87-1.25). There were 261 deaths among those assigned to hormone therapy
and 239 among those assigned to placebo (RH, 1.10; 95% CI, 0.92-1.31). Adjusted
and as-treated analyses did not alter our conclusions.
Conclusions Treatment for 6.8 years with estrogen plus progestin in older women
with coronary disease increased the rates of venous thromboembolism and biliary
tract surgery. Trends in other disease outcomes were not favorable and should
be assessed in larger trials and in broader populations.
INTRODUCTION
The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized,
blinded trial to determine the effects of estrogen plus progestin compared
with placebo in older postmenopausal women with coronary disease. Disease
surveillance continued in HERS II for an additional 2.7 years, during which
many of the women randomized to hormones took open-label estrogen prescribed
by their personal physicians but only a few of those assigned to placebo did.1 During the 6.8 years of observation in HERS and HERS
II combined, we detected no overall effect of hormone therapy on cardiovascular
disease (CVD) event rates.1
Hormone therapy after menopause can have effects on a variety of disease
outcomes. We present data on non-CVD events over this extended period of hormone
therapy. We examine whether the increase in risk of thromboembolic events
observed in hormone-treated women in HERS2
diminishes over time, as observational studies have suggested,3-4
and whether the increased rate of biliary tract surgery that appeared to be
present in hormone-treated women in HERS5 is
confirmed as additional events occur. More generally, we present data on the
effect of hormone therapy on other disease outcomes thought to be associated
with hormone therapy, including fractures, cancer, and total mortality.
METHODS
Study Participants and Baseline Measurements
The design and methods of HERS and HERS II have been described.1, 6-7 Briefly, participants
were postmenopausal women younger than 80 years at baseline with coronary
artery disease and no prior hysterectomy. Among the reasons for exclusion
were a history of deep vein thrombosis or pulmonary embolism, history of breast
cancer, endometrial hyperplasia or cancer, abnormal Papanicolaou (Pap) result,
any hormone use within the past 3 months, and disease judged likely to be
fatal within 4 years.
During the baseline period of HERS we obtained information by questionnaire
and interview, and participants underwent physical examination, including
pelvic examination with Pap smear and endometrial evaluation and screening
mammography. All baseline measures except demographics and health history
were repeated at the final HERS visit, an average of 4 months before enrollment
in HERS II.
Treatment, Follow-up, and Outcomes
During the HERS trial, women were randomly allocated to receive either
0.625 mg/d of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate
or an identical placebo. After stopping blinded medications at the end of
the HERS trial, decisions about whether to undertake open-label hormone therapy
were left to the women and their personal physicians. During HERS II participants
were called at 4-month intervals and asked about hormone therapy and about
symptoms or clinical encounters for possible disease events1;
assessment of lipid-lowering drugs (but not bisphosphonates) was also continued
during HERS II.
Disease events were ascertained and documented using the methods from
the HERS trial.7 For in-hospital nonfatal events
and deaths, we required the hospital discharge summary and the following information:
for pulmonary embolism, clinical signs or symptoms and a positive ventilation/perfusion
scan or imaging result; for deep vein thrombosis, documentation by venography,
impedance plethysmography, or Doppler ultrasound; for biliary tract surgery,
an operative report; for clinical fracture, symptoms and a definite fracture
on radiography; and for cancer, report of a tissue diagnosis. For all deaths
in which clinical documentation was insufficient, we obtained a death certificate.
For out-of-hospital deaths we interviewed the physician and/or next of kin
for a description of the terminal event. Data pertaining to suspected outcome
events were independently reviewed and classified according to the prespecified
criteria used in the HERS trial by 2 physicians at the University of California,
San Francisco Coordinating Center who were blinded to original treatment assignment
and to open-label hormone therapy.1, 6-7
Both the telephone contacts and the documentation of outcomes were carried
out with similar efficiency and completeness in the 2 HERS randomized groups.1 The proportions of all HERS II deaths for which we
obtained clinical documentation beyond a death certificate were 81% among
women originally randomized to hormone therapy and 82% among those randomized
to placebo.
Statistical Analyses
As described,1 the primary analyses (using
SAS version 8.2, SAS Inc, Cary, NC) compared the risk of events among women
assigned to hormone therapy with the risk among women assigned to placebo
using unadjusted, intention-to-treat Cox proportional hazards models for time
to first event. We censored women at the last contact or at loss to follow-up.
In the analyses of biliary tract surgery, we excluded those with a cholecystectomy
prior to enrollment in HERS.
Mortality was assessed in all HERS participants throughout the 6.8 years
of follow-up, but morbidity surveillance during HERS II was limited to the
93% of surviving women who enrolled. To control for confounding, we estimated
the effects of hormone therapy in adjusted Cox models that included all predictors
significant at P<.20 in multivariate analysis.
The 1993-1994 baseline values were used for all variables except statin use,
which was included as a time-dependent covariate. In as-treated adjusted analyses,
women were censored 30 days after they become nonadherent to randomly assigned
treatment, defined as taking less than 80% of their HERS medication or its
equivalent during HERS II.1
RESULTS
The number of women randomized in HERS was 1380 in the hormone therapy
group and 1383 in the placebo group. Of these, 1156 and 1165 enrolled in HERS
II, representing 93% of the 2485 surviving women. Vital status was known for
99.8% of these women at the end of HERS II, with final telephone contacts
completed in 99.5% of known survivors
(see Figure 1 on page 53 of the printed journal).
The mean duration of disease event surveillance
was 6.8 years for women who survived, which included 2.7 years in HERS II.
Risk Factors and Other Characteristics
Table 1 presents risk factors
for non-CVD outcomes using measurements made at the outset of HERS in 1993-1994.
All the variables were equitably distributed between randomized groups for
both the HERS and HERS II cohorts.
|
|
|
|
Table 1. Characteristics of HERS Participants
by Treatment Group*
|
|
|
Treatment With Hormones
Among women randomized to estrogen plus progestin, the proportions reporting
at least 80% adherence to hormone therapy during years 1 through 6 were 81%,
78%, 74%, 67%, 50%, and 45%; comparable proportions for women randomized to
placebo were 0%, 2%, 3%, 3%, 4%, and 8%.
Thromboembolism
There was a 2- to 3-fold increase in incidence of both deep vein thrombosis
and pulmonary embolism in the hormone group during HERS (Table 2). The relative hazard (RH) for deep vein thrombosis was
considerably smaller (1.23) and no longer statistically significant during
HERS II. There was no comparable reduction in RH for pulmonary embolism, although
the number of events available to detect such a time trend was small. When
risk for venous thromboembolism was examined by year of observation (Table 3), the RH declined after the first
2 years, but the time trend was not statistically significant (P = .08).
|
|
|
|
Table 2. Fatal and Nonfatal Noncardiovascular
Events, by Treatment Group*
|
|
|
|
|
|
|
Table 3. Venous Thromboembolic Events by Treatment
Group and Year Since Randomization*
|
|
|
The RH for any venous thromboembolic event over the entire 6.8 years
was 2.08 (95% confidence interval [CI], 1.28-3.40). Event rates were 5.9 per
1000 person-years in the hormone group and 2.8 per 1000 person-years in the
placebo group, an excess of 3.1 per 1000 person-years (P = .003). The number needed to treat (NNT) for 5 years per excess
thromboembolic event is 65 when estimated by intention-to-treat and 50 in
the as-treated analysis. Seven of the 73 women with thromboembolism died within
30 days of the event, and 3 of these deaths were judged due to the event (all
were pulmonary embolisms in women randomized to hormone therapy). Stratifying
the overall findings by baseline aspirin use, the data are weakly consistent
with the hypothesis that aspirin attenuates the adverse effect of hormone
therapy on risk of thromboembolism (RH, 1.68; 95% CI, 0.96-2.92 for aspirin
users; RH, 4.23; 95% CI, 1.41-12.7 for nonusers; interaction P = .14).
Biliary Tract Surgery
The RH for biliary tract surgery in the hormone group compared with
placebo was 1.39 during HERS, 1.70 during HERS II, and 1.48 overall (95% CI,
1.12-1.95) (Table 2). The overall
RH after adjustment for statin use, a statistically significant predictor
of lower rates of biliary tract surgery in our study, was 1.44 (95% CI, 1.10-1.90; P = .01).
The rate of surgery was 19.1 per 1000 person-years in the hormone group,
an excess of 6.2 per 1000 person-years over the placebo group (P = .002). The estimated NNT for 5 years per excess surgery was 32
(intention-to-treat) and 31 (as-treated). Six of the 211 women who had biliary
tract surgery died within 30 days, and 1 of these deaths was judged a consequence
of the surgery.
Cancer
None of the differences between groups in cancer incidence was statistically
significant (Table 2). The overall
RH comparing the hormone and placebo groups was 1.27 (95% CI, 0.84-1.94) for
the 88 breast cancer cases, 1.39 (95% CI, 0.84-2.28) for the 64 lung cancer
cases, and 0.81 (95% CI, 0.46-1.45) for the 47 colon cancer cases. Death due
to these cancers during the period of observation occurred in 3% of women
with breast cancer, 61% of women with lung cancer, and 17% of women with colon
cancer.
Other cancers that occurred in at least 5 women included endometrial
cancer (2 women in the hormone group and 8 in placebo); malignant melanoma
(3 hormone and 5 placebo); lymphoma (7 hormone and 1 placebo); and ovarian
cancer (5 hormone and 2 placebo). The total number of women with any cancer
was 159 in the hormone group vs 135 in the placebo group (RH, 1.19; 95% CI,
0.95-1.50).
Fractures
Women randomized to hormone therapy had more hip fractures than women
randomized to placebo; the overall RH during 6.8 years of observation was
1.61 (95% CI, 0.98-2.66; P = .06) (Table 2). The RH was 1.16 in HERS and 2.11 in HERS II, a difference
that is not statistically significant.
The RH estimates for vertebral, wrist, and other fractures were close
to unity. Based on the total of 452 clinical fractures during 6.8 years of
observation, the RH for any fracture was 1.04 (95% CI, 0.87-1.25). Prevalence
of bisphosphonate use was 2.6% at HERS closeout (in 1998) among women randomized
to hormone therapy and 2.5% among those randomized to placebo.
Mortality
Death rates were high and increasing in this population of older women
with coronary disease. Total mortality in the placebo group was 22 per 1000
person-years during HERS and 38 per 1000 person-years during HERS II (Table 4). The RH for total mortality in
the hormone vs placebo group was 1.06 during HERS, 1.14 during HERS II, and
1.10 overall (95% CI, 0.92-1.31).
|
|
|
|
Table 4. Deaths by Treatment Group*
|
|
|
During the entire 6.8 years of observation, there were 261 deaths in
the hormone group and 239 in the placebo group. Overall, 61% of the deaths
were classified as due to CVD, 19% due to cancer, and 20% due to other cause.
Among the CVD deaths, 132 women in the hormone group and 122 in the placebo
group died of CHD and the remainder died of stroke (23 and 20) and peripheral
arterial disease (4 and 2). Among the cancer deaths, 3 were due to breast
cancer (all in women randomized to hormone therapy). For lung cancer deaths
20 occurred in women randomized to hormone therapy and 19 in those randomized
to placebo; for colon cancer deaths, 2 and 6; and for all other cancer deaths,
26 and 19. Among the non-CVD noncancer deaths, the numbers in the hormone
and placebo groups were 24 and 14 for infectious diseases (including pneumonia
and all forms of sepsis); 15 and 13 for respiratory failure (primarily chronic
obstructive pulmonary disease, excluding pneumonia); 2 and 9 for traumatic
causes, and 10 and 15 for all other causes.
Adjusted and As-Treated Analyses
In addition to the unadjusted intention-to-treat findings described
above, we also estimated the effects of hormone therapy in Cox regression
analyses that adjusted for covariates that were predictors of the outcome.
The purpose was to adjust for imbalances that could have developed because
some women declined to enroll in HERS II. None of the RH estimates was appreciably
altered by the multivariate adjustment (Table 5).
|
|
|
|
Table 5. Overall Relative Hazards of Main
Outcomes Comparing Women Randomized to Hormone Therapy With Those Randomized
to Placebo*
|
|
|
We also carried out analyses restricted to women who remained adherent
to randomly assigned treatment (Table 5). These as-treated RH estimates had wider CIs than the intention-to-treat
estimates due to the smaller numbers of events (40%-73% of the total in the
various models). The as-treated RH for venous thromboembolism was higher than
the unadjusted intention-to-treat value (3.04 vs 2.08 for the overall study);
the as-treated RH was 5.83 during HERS (95% CI, 2.23-15.3) and 0.70 during
HERS II (95% CI, 0.14-3.64). Other as-treated RH estimates in Table 5 differed somewhat from those estimated by intention-to-treat,
but the CIs largely overlapped.
COMMENT
This report examines non-CVD outcomes over a total of 6.8 years of observation
during and following the HERS randomized trial of hormone therapy in postmenopausal
women with coronary disease. We found an increased risk of venous thromboembolism
and biliary tract surgery among women randomized to hormone therapy; rates
of other important disease outcomes were not favorably affected.
Deep Vein Thrombosis and Pulmonary Embolism
HERS2, 7 confirmed reports
from observational studies3, 8-9
that hormone therapy after menopause increases risk of venous thromboembolism.
The estrogen component of HERS treatment is the likely cause because estrogen
without progestin is associated with venous thromboembolism3-4
and selective estrogen receptor modulators also increase the risk.10-11 Risk factors for thromboembolism
in HERS participants included lower extremity fracture, cancer, surgery, and
nonsurgical hospitalization; use of aspirin or statins appeared to be protective.2
HERS participants represent a population at relatively high absolute
risk of deep vein thrombosis or pulmonary embolism. The overall rate in the
placebo group, 2.8 per 1000 person-years, is far higher than that observed
in healthy young postmenopausal women but resembles rates in other populations
of elderly women.3, 12 Therefore
our estimated NNT, 1 excess thromboembolic event among every 50 to 65 women
taking hormones for 5 years, is probably much smaller than it would be for
younger and healthier women.
The longer follow-up available in HERS II suggests that the relative
risk for venous thromboembolic events may decrease after the second year of
hormone therapy (P = .08). Similar decreases over
time have been reported in observational studies of postmenopausal hormone3-4 and oral contraceptive13
use, although there is generally some residual excess risk. A decreasing risk
is plausible, either through attrition of a susceptible subgroup14
or by developing tolerance, and the as-treated analysis suggests that it is
not just due to decreased compliance with hormone therapy during HERS II.
However, the decrease might partly reflect our decision in 1997 (after noting
that venous thromboembolism was more common in hormone-treated women) to emphasize
to study participants the need to stop HERS treatment in the event of fracture,
immobilization, surgery, or cancer.15
Biliary Tract Surgery
Several decades ago the Coronary Drug Project randomized trial found
that high-dose estrogen therapy caused gallbladder disease in men,16 probably due to alteration of the concentration of
cholesterol in the bile,17 and observational
studies of women receiving postmenopausal estrogen have had similar findings.5 We previously reported a 38% higher adjusted rate
of biliary tract surgery in hormone-treated women (P
= .09).5 The longer period of observation reported
here has revealed the increased risk to be statistically significant. Gallbladder
disease was 3 times more common than venous thromboembolism in HERS women,
and the NNT for 5 years to cause 1 excess surgery was 31.
Cancer
Cancer was 19% more common in the hormone therapy group, but the finding
was not statistically significant, nor were there statistically significant
differences in the rates of any specific cancer. The most common of these,
breast cancer, occurred slightly more frequently in the hormone group; the
second most common, lung cancer, also occurred slightly more frequently in
the hormone group; and the third most common, colon cancer, occurred slightly
less often in the hormone group. For each of these 3 cancers, statistically
significant associations in the same direction have been found in observational
studies and biological plausibility has been discussed.18-23
However, the wide CIs and limited duration of follow-up do not permit clear
inferences from these observations of cancer occurrence.
Risk of endometrial cancer was 75% lower among women randomized to hormone
therapy than among those assigned to placebo, but the difference was not statistically
significant. The fact that risk is not increased provides assurance that the
progestin component of HERS treatment prevents the endometrial hyperplasia
and cancer resulting from prolonged use of estrogen.24-25
Fracture
Estrogen is widely believed to prevent osteoporotic fractures. Observational
studies reveal 50% lower fracture rates among women taking hormones than in
women who are not,26-27 and there
is strong clinical trial evidence for a favorable effect of postmenopausal
estrogen treatment, with or without progestin, on bone mineral density in
various populations, including older women.28-29
However, the clinical trial evidence for an effect on fractures has been limited.30-31 Our earlier report from the HERS
main trial revealed little difference between the hormone and placebo groups
in risk of any type of fracture.32 Surprisingly,
the additional follow-up experience from HERS II suggests a risk of hip fracture
among women in the hormone therapy group that is higher than that in the placebo
group. Chance may explain the finding, which does not meet the criteria for
statistical significance, is considerably smaller in the as-treated analysis,
and lacks biological plausibility.
Chance also could play a role in the larger question as to why we did
not observe any reduction in risk of all fractures in the hormone group, although
the confidence interval makes it unlikely that we missed a large benefit.
The absence of routine spine radiographs limited our ability to detect vertebral
fractures. Women studied in HERS were not selected for osteoporosis and are
therefore not well suited to revealing the effects of fracture-prevention
treatments. Clinical trials of bisphosphonates have found an effect on the
risk of fracture in women with osteoporosis, but not in women with normal
bone density.33-34
Mortality
We recorded 261 deaths in the hormone group and 239 in the placebo group.
The absence of mortality benefit contrasts with the finding in observational
studies of lower mortality rates among women who use postmenopausal hormones
compared with nonusers.35-36 Population
differences could underlie this disparity, but we believe that the lower mortality
rate among hormone users in observational studies is primarily due to confounding;
women who seek hormone therapy and remain compliant tend to be healthier and
wealthier than those who do not.37-39
Because these characteristics cannot be measured precisely, their influence
cannot be adequately addressed by statistical adjustment in observational
studies.40
Strengths and Limitations
Clinical trials have shown that short-term hormone therapy after menopause
has favorable effects on surrogate markers for disease, such as blood lipid
levels and bone mineral density, and that it relieves menopausal symptoms
such as hot flushes and insomnia,41-42
but the effects of prolonged hormone therapy in preventing clinical events
have not been established. HERS is the first randomized trial to provide substantial
information on the common disease outcomes that hormones may influence.
HERS II increases the precision of the estimated RHs by adding events
that reflect carryover effects from the randomized treatment phase as well
as the effects of continuation of the originally assigned treatment. About
50% of the hormone group used open-label treatment during HERS II compared
with less than 10% of the placebo group. Those women who did not continue
their randomly assigned treatment (crossovers) diminish the power to observe
effects of the randomized treatment but do not alter the fundamental value
of randomization. To take advantage of this value, our primary analytic approach
was an intention-to-treat comparison of outcomes measured over the entire
6.8 years. However, we also examined the findings with as-treated analyses
to compensate for the effects of crossing over and with adjusted analyses
to compensate for baseline differences resulting from the 7% of women who
did not enroll in HERS II. The as-treated and adjusted findings differ somewhat
from those of intention-to-treat, but the overall conclusions are not altered.
Inferences about the effects of randomized treatments are also contingent
on avoiding unintended interventions applied disproportionately to one randomized
group. Randomized assignment was no longer blinded in HERS II, so at the HERS
closeout visit and in subsequent telephone calls we provided a neutral message
to all women and left advice on hormone use and other preventive treatments
to their personal physicians. We also took steps to prevent bias in the ascertainment
of outcomes by choosing disease events that were objective and by maintaining
the HERS systems for obtaining records and for blinded adjudication. The success
of efforts to avoid between-group bias is supported by the comparability in
the timing and completeness with which the telephone contacts were made and
clinical event data collected.1
Important limitations of HERS stem from the older age of HERS participants,
who averaged 67 years at baseline and 74 years at the end of HERS II, the
presence of coronary disease on entry, and the particular estrogen and progestin
that we chose to study. These characteristics limit generalizability, and
the effects of other hormones in younger, healthier postmenopausal women may
be different. Further information on the effects of hormone therapy on disease
outcomes in healthy postmenopausal women will be available at the conclusion
of the Women's Health Initiative randomized trial.43
CONCLUSIONS
Treatment with estrogen plus progestin in older women with coronary
disease increased the rates of venous thromboembolism and biliary tract surgery
and did not produce favorable trends in overall rates of CVD,1
fracture, or death. Postmenopausal hormone therapy should be limited to indications
that are supported by randomized trial evidence that beneficial clinical outcomes
outweigh harmful ones.
AUTHOR INFORMATION
Financial Disclosures: During the conduct of
HERS, all authors were supported by contracts from Wyeth-Ayerst. Dr Barrett-Connor
has received research funding from Eli Lilly and Merck, and has served on
an advisory board for Wyeth-Ayerst; Dr Cauley has received research funding
from Eli Lilly, Merck, and Pfizer, and honoraria from Eli Lilly and Procter
and Gamble; Dr Grady has received research funding from Berlex and Eli Lilly;
Dr Knopp has received research funding and/or speaking honoraria from Abbott,
AstraZeneca, Bristol-Myers Squibb, Kos, Merck, Ortho-McNeil Pharmaceuticals,
and Pfizer; and Dr Satterfield has received research funding from Eli Lilly,
Merck, and Pfizer.
Author Contributions: Dr Hulley, as principal
investigator of the HERS II study, had full access to all of the data in the
study and takes responsibility for the integrity of the data and the accuracy
of the data analyses.
Study concept and design: Hulley, Grady, Furberg,
Barrett-Connor, Cauley, Haskell, Knopp, Schrott, Vittinghoff, Hunninghake.
Acquisition of data: Hulley, Grady, Furberg,
Barrett-Connor, Cauley, Haskell, Knopp, Lowery, Satterfield, Schrott, Vittinghoff,
Hunninghake.
Analysis and interpretation of data: Hulley,
Furberg, Barrett-Connor, Cauley, Grady, Haskell, Knopp, Lowery, Satterfield,
Schrott, Vittinghoff, Hunninghake.
Drafting of the manuscript: Hulley, Grady,
Vittinghoff, Barrett-Connor.
Critical revision of the manuscript for important
intellectual content: Hulley, Furberg, Barrett-Connor, Cauley, Grady,
Haskell, Knopp, Lowery, Satterfield, Schrott, Vittinghoff, Hunninghake.
Statistical expertise: Vittinghoff.
Obtained funding: Hulley, Furberg, Barrett-Connor,
Cauley, Grady, Haskell, Knopp, Lowery, Satterfield, Schrott, Vittinghoff,
Hunninghake.
Administrative, technical, or material support:
Hulley, Furberg, Barrett-Connor, Cauley, Grady, Haskell, Knopp, Lowery, Satterfield,
Schrott, Vittinghoff, Hunninghake.
Study supervision: Hulley, Furberg, Grady.
Role of the Sponsor: Wyeth-Ayerst Research
funded the study, contributed to its design, oversaw quality control at the
clinical centers, including periodic site visits, and edited the data collected
by the clinical centers (except for disease outcome data) before sending it
to the coordinating center at UCSF. The sponsor did not have access to the
blinding code and played no role in collecting or adjudicating disease outcomes
nor in data analysis. The sponsor had the opportunity to review and comment
on manuscripts written by the investigators, but our contract gave the investigators
the final decision regarding content.
Funding/Support: This study was funded by Wyeth-Ayerst
Research.
Clinical Center Investigators: Baylor College
of Medicine, Houston, Tex: Alan Herd, MD, Melissa Kulkarni, RN; Cedars-Sinai
Medical Center, Los Angeles, Calif: Steven Khan, MD, T. Keta Hodgson, BSN;
Chicago Center for Clinical Research, Chicago, Ill: Michael Davidson, MD,
Marlene Wentworth, RN; Duke University Medical Center, Durham, NC: Kristin
Newby, MD, Rose Marie Smigla, RN; Emory University, Atlanta, Ga: Nanette K.
Wenger, MD, Sally McNagny, MD, MPH, Janice Parrott, RN, Dana Drummond; George
Washington University, Washington, DC: Judith Hsia, MD, Ginny Levin, MPH,
Donna Embersit; Hartford Hospital, Hartford, Conn: David Waters, MD, Paul
Thompson, MD, Jennifer DeDominicis, BSN, Marilyn Siwy, RN; Johns Hopkins University,
Baltimore, Md: Trudy Bush, PhD, Roger S. Blumenthal, MD, Susan R. Miller,
MPH, DSc, Katherine Bass, MD, MHS, Janice Huth, Teresa Greene; Northwest Lipid
Research Clinic, Seattle, Wash: Robert H. Knopp, MD, Barbara Twaddell, RN;
Stanford University, Palo Alto, Calif: William L. Haskell, PhD, Kathy Berra,
MSN, ANP, Laurie Ausserer, BS; University of Alabama, Birmingham: William
J. Rogers, MD, Vera Bittner, MD, R. Edward Varner, MD, Glenda Blackburn, LPN;
University of California, San Diego: Elizabeth Barrett-Connor, MD, Cynthia
A. Stuenkel, MD, Sue Hawley, BSN, RN; University of Iowa, Iowa City: Helmutt
Schrott, MD, Diane Meyerholz, RN; University of Miami, Miami, Fla: Maureen
Lowery, MD, Jose A. Martel, MPH; University of Minnesota, Minneapolis: Donald
Hunninghake, MD, Jean Olson, RN, Larry Kotek, MD, Sue Krook, PhD; University
of Pittsburgh, Pittsburgh, Pa (2 sites): Jane A. Cauley, DrPH, Alan Goodman,
MD, Robert McDonald, Jr, MD, Karen Southwick, Sheree Schaffer, Michelle Boyd,
RN, MS; University of Tennessee, Memphis: Suzanne Satterfield, MD, Karen C.
Johnson, MD, Beth McCammon, RN; Wake Forest University, Winston-Salem and
Greensboro, NC (2 sites): David Herrington, MD, MHS, Karen Blinson, BS, Marcia
Davis, BSN, Vickie Wayne, RN, Lynda Doomy, Kay Cheshire, MEd, Mary Boozer,
LPN, Judy Iannuzzi, BSN.
Coordinating Center: University of California,
San Francisco: Stephen Hulley, MD, MPH, Deborah Grady, MD, MPH, Eric Vittinghoff,
PhD, Joel Simon, MD, MPH, Lily Chaput, MD, MPH, Michael Shlipak, MD, MPH,
Feng Lin MS, Christine C. Ireland, MPH, Judith Macer, BS. Executive Committee: Stephen Hulley, MD (chair), Curt Furberg, MD,
PhD (co-chair), Vera Bittner, MD, Ginger Constantine, MD, Deborah Grady, MD,
David Herrington, MD, Donald Hunninghake, MD, Nanette Wenger, MD. HERS II Data Review Committee: Stephen Hulley, MD (chair), Deborah
Grady, MD, Eric Vittinghoff, PhD, Curt Furberg, MD, PhD, Robert Levy, Ginger
Constantine, MD.
Acknowledgment: We thank Steven Cummings, MD,
for help with designing and interpreting the study.
Corresponding Author and Reprints: Stephen
Hulley, MD, MPH, University of California, San Francisco, San Francisco, CA
94143-0560 (e-mail: shulley{at}epi.ucsf.edu).
Author Affiliations: Department of Epidemiology
and Biostatistics, School of Medicine, University of California, San Francisco
(Drs Hulley, Grady, and Vittinghoff); Department of Public Health Sciences,
Wake Forest University School of Medicine, Winston-Salem, NC (Dr Furberg);
Division of Epidemiology, Department of Family and Preventive Medicine, University
of California, San Diego (Dr Barrett-Connor); Department of Epidemiology,
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa
(Dr Cauley); Department of Medicine, Stanford University, Stanford, Calif
(Dr Haskell); Department of Medicine, University of Washington School of Medicine,
Seattle (Dr Knopp); University of Miami School of Medicine, Miami, Fla (Dr
Lowery); Department of Preventive Medicine, University of Tennessee, Memphis
(Dr Satterfield); College of Public Health and Medicine, University of Iowa,
Iowa City (Dr Schrott); and Departments of Medicine and Pharmacology, University
of Minnesota, Minneapolis (Dr Hunninghake).
REFERENCES
| |
1. Grady D, Herrington D, Bittner V, et al for the HERS Research Group. Cardiovascular disease outcomes during 6.8 years of hormone therapy:
Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002;288:49-57.
FREE FULL TEXT
2. Grady D, Wenger NK, Herrington D, et al. Postmenopausal hormone therapy increases risk for venous thromboembolic
disease: the Heart and Estrogen/progestin Replacement Study. Ann Intern Med. 2000;132:689-696.
FREE FULL TEXT
3. Daly E, Vessey MP, Hawkins MM, Carson JL, Gough P, Marsh S. Risk of venous thromboembolism in users of hormone replacement therapy. Lancet. 1996;348:977-980.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
4. Perez Gutthann S, Garcia Rodriguez LA, Castellsague J, Duque Oliart A. Hormone replacement therapy and risk of venous thromboembolism: population
based case-control study. BMJ. 1997;314:796-800.
FREE FULL TEXT
5. Simon JA, Hunninghake DB, Agarwal SK, et al for the Heart and Estrogen/progestin Replacement Study. Effect of estrogen plus progestin on risk for biliary tract surgery
in postmenopausal women with coronary artery disease. Ann Intern Med. 2001;135:493-501.
FREE FULL TEXT
6. Grady D, Applegate W, Bush T, Furberg C, Riggs B, Hulley SB. Heart and Estrogen/progestin Replacement Study (HERS): design, methods,
and baseline characteristics. Control Clin Trials. 1998;19:314-335.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
7. Hulley S, Grady D, Bush T, et al for the Heart and Estrogen/progestin Replacement Study (HERS) Research
Group. Randomized trial of estrogen plus progestin for secondary prevention
of coronary heart disease in postmenopausal women. JAMA. 1998;280:605-613.
FREE FULL TEXT
8. Jick H, Derby LE, Myers MW, Vasilakis C, Newton KM. Risk of hospital admission for idiopathic venous thromboembolism among
users of postmenopausal oestrogens. Lancet. 1996;348:981-983.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
9. Grodstein F, Stampfer MJ, Goldhaber SZ, et al. Prospective study of exogenous hormones and risk of pulmonary embolism
in women. Lancet. 1996;348:983-987.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
10. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical
Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90:1371-1388.
FREE FULL TEXT
11. Cummings SR, Eckert S, Krueger KA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal
women: results from the MORE randomized trial. JAMA. 1999;281:2189-2197.
FREE FULL TEXT
12. Nordstrom M, Lindblad B, Bergqvist D, Kjellstrom T. A prospective study of the incidence of deep-vein thrombosis within
a defined urban population. J Intern Med. 1992;232:155-160.
WEB OF SCIENCE
| PUBMED
13. Vandenbroucke JP, Rosing J, Bloemenkamp KWM, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med. 2001;344:1527-1533.
FREE FULL TEXT
14. Psaty BM, Smith NL, Lemaitre RN, et al. Hormone replacement therapy, prothrombotic mutations, and the risk
of incident nonfatal myocardial infarction in postmenopausal women. JAMA. 2001;285:906-913.
FREE FULL TEXT
15. Grady D, Hulley SB, Furberg C. Venous thromboembolic events associated with hormone replacement therapy. JAMA. 1997;278:477.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
16. CDP Research Group. Gallbladder disease as a side effect of drugs influencing lipid metabolism:
experience in the Coronary Drug Project. N Engl J Med. 1977;296:1185-1190.
ABSTRACT
17. Johnston DE, Kaplan MM. Pathogenesis and treatment of gallstones. N Engl J Med. 1993;328:412-421.
FREE FULL TEXT
18. CDP Research Group. Findings leading to discontinuation of the 2.5 mg/day estrogen group. JAMA. 1973;226:652-657.
FREE FULL TEXT
19. Clemons M, Goss P. Estrogen and the risk of breast cancer. N Engl J Med. 2001;344:276-285.
FREE FULL TEXT
20. Colditz GA. Hormone replacement therapy increases the risk of breast cancer. Ann N Y Acad Sci. 1997;833:129-136.
WEB OF SCIENCE
| PUBMED
21. Collaborative Group. Breast cancer and hormone replacement therapy: collaborative reanalysis
of data from 51 epidemiological studies of 52,705 women with breast cancer
and 108,411 women without breast cancer. Lancet. 1997;350:1047-1059.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
22. Siegfried JM. Women and lung cancer: does oestrogen play a role? Lancet Oncol. 2001;2:506-513.
FULL TEXT
| PUBMED
23. Grodstein F, Newcomb PA, Stampfer MJ. Postmenopausal hormone therapy and the risk of colorectal cancer: a
review and meta-analysis. Am J Med. 1999;106:574-582.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
24. Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol. 1995;85:304-313.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
25. Burkman RT, Collins JA, Shulman LP, Williams JK. Current perspectives on oral contraceptive use. Br J Haematol. 2001;115:415-420.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
26. Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal
women. Ann Intern Med. 1992;117:1016-1037.
FREE FULL TEXT
27. Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR. Estrogen replacement therapy and fractures in older women: Study of
Osteoporotic Fractures. Ann Intern Med. 1995;122:9-16.
FREE FULL TEXT
28. PEPI Writing Group. Effects of hormone therapy on bone mineral density: results from the
Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. JAMA. 1996;276:1389-1396.
FREE FULL TEXT
29. Villareal DT, Binder EF, Williams DB, Schechtman KB, Yarasheski KE, Kohrt WM. Bone mineral density response to estrogen replacement in frail elderly
women: a randomized controlled trial. JAMA. 2001;286:815-820.
FREE FULL TEXT
30. Torgerson DJ, Bell-Syer SEM. Does hormone replacement therapy prevent nonvertebral fractures: a
review of randomized trials and meta-analysis. JAMA. 2001;285:2891-2897.
FREE FULL TEXT
31. Grady D, Cummings SR. Postmenopausal hormone therapy for prevention of fractures: how good
is the evidence? JAMA. 2001;285:2909-2910.
FREE FULL TEXT
32. Cauley JA, Black DM, Barrett-Connor E, et al. Effects of hormone replacement therapy on clinical fractures and height
loss: the Heart and Estrogen/progestin Replacement Study (HERS). Am J Med. 2001;110:442-450.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
33. Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density
but without vertebral fractures: results from the Fracture Intervention Trial. JAMA. 1998;280:2077-2082.
FREE FULL TEXT
34. McClung MR, Geusens P, Miller PD. Effect of risedronate on the risk of hip fracture in elderly women:
HIP Intervention Program. N Engl J Med. 2001;344:333-340.
FREE FULL TEXT
35. Bush TL, Barrett-Connor E, Cowan LD, et al. Cardiovascular mortality and noncontraceptive use of estrogen in women:
results from the Lipid Research Clinics Program Follow-up Study. Circulation. 1987;75:1102-1109.
FREE FULL TEXT
36. Grodstein F, Stampfer MJ, Colditz GA, et al. Postmenopausal hormone therapy and mortality. N Engl J Med. 1997;336:1769-1775.
FREE FULL TEXT
37. Barrett-Connor E. Postmenopausal estrogen and prevention bias. Ann Intern Med. 1991;115:455-456.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
38. Petitti DB. Coronary heart disease and estrogen replacement therapy: can compliance
bias explain the results of observational studies? Ann Epidemiol. 1994;4:115-118.
PUBMED
39. Matthews KA, Kuller LH, Wing RR, Meilahn EN, Plantinga P. Prior to use of estgrogen replacement therapy, are users healthier
than nonusers? Am J Epidemiol. 1996;143:971-978.
FREE FULL TEXT
40. Grady D, Hulley S. Hormones to prevent coronary disease in women: when are observational
studies adequate evidence? Ann Intern Med. 2000;133:999-1001.
FREE FULL TEXT
41. Greendale G, Reboussin B, Hogan P, et al. Symptom relief and side effects of postmenopausal hormones: results
from the Postmenopausal Estrogen/Progestin Interventions Trial. Obstet Gynecol. 1998;92:982-988.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
42. MacLennan A, Lester S, Moore V. Oral estrogen replacement therapy versus placebo for hot flushes: a
systematic review. Climacteric. 2001;4:58-74.
PUBMED
43. WHI Study Group. Design of the Women's Health Initiative clinical trial and observational
study. Control Clin Trials. 1998;19:61-109.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLES
Cardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy: Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II)
Deborah Grady, David Herrington, Vera Bittner, Roger Blumenthal, Michael Davidson, Mark Hlatky, Judith Hsia, Stephen Hulley, Alan Herd, Steven Khan, L. Kristin Newby, David Waters, Eric Vittinghoff, Nanette Wenger, and for the HERS Research Group
JAMA. 2002;288(1):49-57.
ABSTRACT
| FULL TEXT
Hormone Replacement Therapy for Prevention: More Evidence, More Pessimism
Diana B. Petitti
JAMA. 2002;288(1):99-101.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores
Hippisley-Cox and Coupland
BMJ 2009;339:b4229-b4229.
ABSTRACT
| FULL TEXT
Combined Hormone Therapy at Menopause and Breast Cancer: A Warning--Short-Term Use Increases Risk
Bernstein
JCO 2009;27:5116-5119.
FULL TEXT
Current Impediments to Acceptance of the Ultraviolet-B-Vitamin D-Cancer Hypothesis
GRANT and BOUCHER
Anticancer Res 2009;29:3597-3604.
ABSTRACT
| FULL TEXT
Women's Issues in Pulmonary Medicine
Levine
ACCP Pulmonary Med Brd Rev 2009;25:705-722.
FULL TEXT
Reassessing Benefits and Risks of Hormone Therapy
Gass et al.
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2009;3:29-43.
ABSTRACT
Conjugated Equine Estrogens and Colorectal Cancer Incidence and Survival: The Women's Health Initiative Randomized Clinical Trial
Ritenbaugh et al.
Cancer Epidemiol. Biomarkers Prev. 2008;17:2609-2618.
ABSTRACT
| FULL TEXT
Testosterone and the breast
Shufelt and Braunstein
Menopause Int 2008;14:117-122.
ABSTRACT
| FULL TEXT
Venous thromboembolism in women
Rathbun
Vasc Med 2008;13:255-266.
ABSTRACT
Dose-dependent cardiac effect of oestrogen replacement in mice post-myocardial infarction
Zhan et al.
Exp Physiol 2008;93:982-993.
ABSTRACT
| FULL TEXT
Invited Commentary: Postmenopausal Unopposed Estrogen and Breast Cancer Risk in the Women's Health Initiative--Before and Beyond
Linet
Am J Epidemiol 2008;167:1416-1420.
ABSTRACT
| FULL TEXT
Health Risks and Benefits 3 Years After Stopping Randomized Treatment With Estrogen and Progestin
Heiss et al.
JAMA 2008;299:1036-1045.
ABSTRACT
| FULL TEXT
Devices for home evaluation of women's health concerns
Scolaro et al.
Am J Health Syst Pharm 2008;65:299-314.
ABSTRACT
| FULL TEXT
Menopause hormone replacement therapy and cancer risk: an Italian record linkage investigation
Corrao et al.
Ann Oncol 2008;19:150-155.
ABSTRACT
| FULL TEXT
Age and Menopausal Effects of Hormonal Birth Control and Hormone Replacement Therapy in Relation to Breast Cancer Risk
Shantakumar et al.
Am J Epidemiol 2007;165:1187-1198.
ABSTRACT
| FULL TEXT
Case-Control Study of Postmenopausal Hormone Replacement Therapy and Endometrial Cancer
Strom et al.
Am J Epidemiol 2006;164:775-786.
ABSTRACT
| FULL TEXT
Duration not severity of the climacteric syndrome predicts resumption of hormone therapy after discontinuation: a prospective cohort study
Haimov-Kochman et al.
Hum Reprod 2006;21:2450-2454.
ABSTRACT
| FULL TEXT
Advancing the Study of Stroke in Women: Summary and Recommendations for Future Research From an NINDS-Sponsored Multidisciplinary Working Group
Bushnell et al.
Stroke 2006;37:2387-2399.
ABSTRACT
| FULL TEXT
Natural Health Products in the Prevention and Treatment of Osteoporosis: Systematic Review of Randomized Controlled Trials
Whelan et al.
The Annals of Pharmacotherapy 2006;40:836-849.
ABSTRACT
| FULL TEXT
A prospective study of female hormone use and breast cancer among black women.
Rosenberg et al.
Arch Intern Med 2006;166:760-765.
ABSTRACT
| FULL TEXT
Emerging and widening colorectal carcinoma disparities between blacks and whites in the United States (1975-2002).
Irby et al.
Cancer Epidemiol. Biomarkers Prev. 2006;15:792-797.
ABSTRACT
| FULL TEXT
Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials
Greiser et al.
Hum Reprod Update 2005;11:561-573.
ABSTRACT
| FULL TEXT
Breast cancer risk with postmenopausal hormonal treatment
Collins et al.
Hum Reprod Update 2005;11:545-560.
ABSTRACT
| FULL TEXT
Hormone replacement therapy: pathobiological aspects of hormone-sensitive cancers in women relevant to epidemiological studies on HRT: a mini-review
Dietel et al.
Hum Reprod 2005;20:2052-2060.
ABSTRACT
| FULL TEXT
Breast cancer incidence, case-fatality and breast cancer mortality in Danish women using hormone replacement therapy--a prospective observational study
Stahlberg et al.
Int J Epidemiol 2005;34:931-935.
FULL TEXT
Women's Health: A Call for Papers
DeAngelis and Glass
JAMA 2005;293:2662-2662.
FULL TEXT
Hormone Therapy for the Prevention of Chronic Conditions in Postmenopausal Women: Recommendations from the U.S. Preventive Services Task Force
U.S. Preventive Services Task Force*
ANN INTERN MED 2005;142:855-860.
ABSTRACT
| FULL TEXT
Correlating Androgen and Estrogen Steroid Receptor Expression with Coronary Calcification and Atherosclerosis in Men without Known Coronary Artery Disease
Liu et al.
J. Clin. Endocrinol. Metab. 2005;90:1041-1046.
ABSTRACT
| FULL TEXT
Risk Factors for Estrogen Receptor-Positive Breast Cancer
Hwang et al.
Arch Surg 2005;140:58-62.
ABSTRACT
| FULL TEXT
Venous Thrombosis: The Role of Genes, Environment, and Behavior
Rosendaal
ASH Education Book 2005;2005:1-12.
ABSTRACT
| FULL TEXT
E4F1, a Novel Estrogen-Responsive Gene in Possible Atheroprotection, Revealed by Microarray Analysis
Nakamura et al.
Am. J. Pathol. 2004;165:2019-2031.
ABSTRACT
| FULL TEXT
Hormone Therapy: Making Decisions in the Face of Uncertainty
Peterson et al.
Arch Intern Med 2004;164:2308-2312.
FULL TEXT
Management of the Elderly Person After Myocardial Infarction
Aronow
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2004;59:1173-1185.
ABSTRACT
| FULL TEXT
Risk of Venous Thromboembolic Disease Associated With Hormonal Contraceptives and Hormone Replacement Therapy: A Clinical Review
Gomes and Deitcher
Arch Intern Med 2004;164:1965-1976.
ABSTRACT
| FULL TEXT
Estrogen Plus Progestin and Risk of Venous Thrombosis
Cushman et al.
JAMA 2004;292:1573-1580.
ABSTRACT
| FULL TEXT
Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification
Doherty et al.
Endocr. Rev. 2004;25:629-672.
ABSTRACT
| FULL TEXT
National Trends in Osteoporosis Visits and Osteoporosis Treatment, 1988-2003
Stafford et al.
Arch Intern Med 2004;164:1525-1530.
ABSTRACT
| FULL TEXT
Prevalence of Prevention and Treatment Modalities Used in Populations at Risk of Osteoporosis
Rohr et al.
JAOA: Journal of the American Osteopathic Association 2004;104:281-287.
ABSTRACT
| FULL TEXT
Hormones and breast cancer
ESHRE Capri Workshop Group
Hum Reprod Update 2004;10:281-293.
ABSTRACT
| FULL TEXT
Lifestyle and Demographic Factors in Relation to Vasomotor Symptoms: Baseline Results from the Study of Women's Health Across the Nation
Gold et al.
Am J Epidemiol 2004;159:1189-1199.
ABSTRACT
| FULL TEXT
Recognizing and Treating Glucocorticoid-Induced Osteoporosis in Patients With Pulmonary Diseases
Gluck and Colice
Chest 2004;125:1859-1876.
ABSTRACT
| FULL TEXT
Postmenopausal Estrogen for Treatment of Hot Flashes: Clinical Applications
Nelson
JAMA 2004;291:1621-1625.
ABSTRACT
| FULL TEXT
Current Management of Urinary Incontinence
Knight-Klimas
Journal of Pharmacy Practice 2004;17:103-114.
ABSTRACT
Estrogen plus Progestin and Colorectal Cancer in Postmenopausal Women
Chlebowski et al.
NEJM 2004;350:991-1004.
ABSTRACT
| FULL TEXT
Women's Ischemic Syndrome Evaluation: Current Status and Future Research Directions Report of the National Heart, Lung and Blood Institute Workshop : October 2-4, 2002 : Section 4: Lessons From Hormone Replacement Trials
Waters et al.
Circulation 2004;109
:e53-e55.
FULL TEXT
Benefits and harms associated with hormone replacement therapy: clinical decision analysis
Minelli et al.
BMJ 2004;328:371.
ABSTRACT
| FULL TEXT
Hormone Replacement Therapy Is Associated with Less Coronary Atherosclerosis in Postmenopausal Women
Akhrass et al.
J. Clin. Endocrinol. Metab. 2003;88:5611-5614.
ABSTRACT
| FULL TEXT
Menopause in crisis post-Women's Health Initiative? A view based on personal clinical experience
Neves-e-Castro
Hum Reprod 2003;18:2512-2518.
ABSTRACT
| FULL TEXT
The Combination of a Novel Selective Estrogen Receptor Modulator with an Estrogen Protects the Mammary Gland and Uterus in a Rodent Model: The Future of Postmenopausal Women's Health?
Labrie et al.
Endocrinology 2003;144:4700-4706.
ABSTRACT
| FULL TEXT
Effects of Estrogen Plus Progestin on Risk of Fracture and Bone Mineral Density: The Women's Health Initiative Randomized Trial
Cauley et al.
JAMA 2003;290:1729-1738.
ABSTRACT
| FULL TEXT
Effects of Estrogen Plus Progestin on Gynecologic Cancers and Associated Diagnostic Procedures: The Women's Health Initiative Randomized Trial
Anderson et al.
JAMA 2003;290:1739-1748.
ABSTRACT
| FULL TEXT
Issues to debate on the Women's Health Initiative (WHI) study. Hormone replacement therapy: an epidemiological dilemma?
Machens and Schmidt-Gollwitzer
Hum Reprod 2003;18:1992-1999.
ABSTRACT
| FULL TEXT
Drug Therapy for Prevention of Recurrent Myocardial Infarction
van der Elst et al.
The Annals of Pharmacotherapy 2003;37:1465-1477.
ABSTRACT
| FULL TEXT
Registering Clinical Trials
Dickersin and Rennie
JAMA 2003;290:516-523.
ABSTRACT
| FULL TEXT
Phytoestrogen Supplements for the Treatment of Hot Flashes: The Isoflavone Clover Extract (ICE) Study: A Randomized Controlled Trial
Tice et al.
JAMA 2003;290:207-214.
ABSTRACT
| FULL TEXT
Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women: The Women's Health Initiative Randomized Trial
Chlebowski et al.
JAMA 2003;289:3243-3253.
ABSTRACT
| FULL TEXT
Estrogen Increases Bone Marrow-Derived Endothelial Progenitor Cell Production and Diminishes Neointima Formation
Strehlow et al.
Circulation 2003;107:3059-3065.
ABSTRACT
| FULL TEXT
Female Sexual Dysfunction: Review of the Disorder and Evidence for Available Treatment Alternatives
Miller and Hunt
Journal of Pharmacy Practice 2003;16:200-208.
ABSTRACT
Combination Therapy With Hormone Replacement and Alendronate for Prevention of Bone Loss in Elderly Women: A Randomized Controlled Trial
Greenspan et al.
JAMA 2003;289:2525-2533.
ABSTRACT
| FULL TEXT
Evaluating Therapeutic Modalities for Prevention and Treatment of Postmenopausal Osteoporosis
Sagraves
The Annals of Pharmacotherapy 2003;37:744-746.
FULL TEXT
Dietary Soy Protein Maintains Some Indices of Bone Mineral Density and Bone Formation in Aged Ovariectomized Rats
Blum et al.
J. Nutr. 2003;133:1244-1249.
ABSTRACT
| FULL TEXT
Estrogen and testosterone have opposing effects on chronic cardiac remodeling and function in mice with myocardial infarction
Cavasin et al.
Am. J. Physiol. Heart Circ. Physiol. 2003;284:H1560-H1569.
ABSTRACT
| FULL TEXT
Risks and benefits of hormone replacement therapy: The evidence speaks
Humphries and Gill
CMAJ 2003;168:1001-1010.
ABSTRACT
| FULL TEXT
Soy Protein Has a Greater Effect on Bone in Postmenopausal Women Not on Hormone Replacement Therapy, as Evidenced by Reducing Bone Resorption and Urinary Calcium Excretion
Arjmandi et al.
J. Clin. Endocrinol. Metab. 2003;88:1048-1054.
ABSTRACT
| FULL TEXT
Making decisions about hormone replacement therapy
Rymer et al.
BMJ 2003;326:322-326.
FULL TEXT
Current Use of Unopposed Estrogen and Estrogen Plus Progestin and the Risk of Acute Myocardial Infarction Among Women With Diabetes: The Northern California Kaiser Permanente Diabetes Registry, 1995-1998
Ferrara et al.
Circulation 2003;107:43-48.
ABSTRACT
| FULL TEXT
Long term oestrogen plus progestin increased venous thromboembolism and biliary tract surgery in postmenopausal women
Atkins
Evid. Based Med. 2003;8:13-13.
FULL TEXT
OTHER ARTICLES NOTED (Nov 01 to 18 Oct 02)
Evid. Based Nurs. 2003;6:e1-1.
FULL TEXT
Effectiveness of Estrogen Replacement in Restoration of Cognitive Function after Long-Term Estrogen Withdrawal in Aging Rats
Markowska and Savonenko
J. Neurosci. 2002;22:10985-10995.
ABSTRACT
| FULL TEXT
Postmenopausal Hormone Replacement Therapy for Primary Prevention of Chronic Conditions: Recommendations and Rationale
U.S. Preventive Services Task Force*
ANN INTERN MED 2002;137:834-839.
ABSTRACT
| FULL TEXT
Osteoporosis and Fractures in Postmenopausal Women Using Estrogen
Nelson et al.
Arch Intern Med 2002;162:2278-2284.
ABSTRACT
| FULL TEXT
Pathophysiology and Treatment of Hot Flashes
Shanafelt et al.
Mayo Clin Proc. 2002;77:1207-1218.
ABSTRACT
No Long-Term Secondary-Prevention Benefit with Combination HRT
Journal Watch Cardiology 2002;2002:2-2.
FULL TEXT
Postmenopausal Hormone Replacement Therapy: Scientific Review
Nelson et al.
JAMA 2002;288:872-881.
ABSTRACT
| FULL TEXT
Assessing Benefits and Harms of Hormone Replacement Therapy: Clinical Applications
Nelson
JAMA 2002;288:882-884.
ABSTRACT
| FULL TEXT
HERS II: Continued Lack of Benefit with Estrogen/Progestin
JWatch Women's Health 2002;2002:2-2.
FULL TEXT
Estrogen/Progestin Replacement in Older Women with Coronary Disease: No Benefit
JWatch General 2002;2002:1-1.
FULL TEXT
Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled Trial
Writing Group for the Women's Health Initiative In
JAMA 2002;288:321-333.
ABSTRACT
| FULL TEXT
Estrogen Replacement Therapy and Risk of Ovarian Cancer
Noller
JAMA 2002;288:368-369.
FULL TEXT
Cardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy: Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II)
Grady et al.
JAMA 2002;288:49-57.
ABSTRACT
| FULL TEXT
Hormone Replacement Therapy for Prevention: More Evidence, More Pessimism
Petitti
JAMA 2002;288:99-101.
FULL TEXT
|
