Volume 17, Issue 1
Winter 2005
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CHS Research News
Vol 17, Issue 1, Winter 2005
Center News
by Joan DeClaire
New Findings
Bone density returns when teens stop using
popular contraceptive
A new study of the popular injectable contraceptive Depo-Provera shows that
teenagers’ bone density recovers after they stop using the drug. Several
previous studies have linked Depo-Provera to bone loss, raising concerns about
its use among teens, a population in their peak bone-building years.
"These findings are reassuring for those concerned about future risk
of fractures," said Delia Scholes, PhD, senior investigator at Group
Health Center for Health Studies and the study’s lead
investigator. "This information can be useful in helping young women
balance the need to avoid unintended pregnancies with the need to build strong
bones."
Scholes’ study, which appears in the February 2005 issue of Archives
of Pediatric and Adolescent Medicine, is the first to show that teen-aged
Depo-Provera users’ bone loss appears to be reversed once young women stop
taking the contraceptive. The findings come less than three months after a
decision by the U.S. Food and Drug Administration to issue a black box warning
on Depo-Provera. The warning states that the drug is associated with bone loss
that "may not be completely reversible."
While Scholes and her colleagues found that Depo-Provera use in women aged
14 to 18 was associated with continuous bone density loss at the hip and
spine, they also found that users experienced significant gains after they
quit using the drug. This provides evidence "that the loss of bone mass
is apparently reversed," Scholes concluded.
In 2002, Scholes reported similar results among women aged 18 to 39.
However, the current study shows that teen women who discontinued using
Depo-Provera appeared to regain their bone density faster than older women
did.
Teens use Depo-Provera at higher rates than older women do. About 10
percent of American women aged 15 to 19 who are using birth control use
Depo-Provera, compared to just 3 percent of women in the United States
overall. Given once every three months, the method is effective, relatively
low in cost, private, and easy-to-use, Scholes explained. It is also a popular
choice among young women for whom other types of contraception have failed.
How the study was conducted
The researchers measured hip, spine, and whole-body bone densities in 170
healthy teen women, aged 14 to 18, who get their care at Group Health
Cooperative. The bone densities of the 80 participants receiving Depo-Provera
injections were compared to those of 90 similar women who were not using this
method. Bone density measurements were taken at the start of the study, and at
6-month intervals over a span of 2 to 3 years. During that period, 61 of the
Depo-Provera users stopped using the drug, allowing the scientists to see how
their bone density changed once they discontinued.
What the researchers found
As with previous studies, the researchers found that, compared to
non-users, Depo-Provera users had significant loss of bone density in the hip
and spine.
- Those who used Depo-Provera experienced an average loss of bone density
at the hip of 1.81 percent per year compared with a loss of 0.19 percent
per year among non-users.
- At the spine, women who used Depo-Provera had a bone loss of 0.97
percent, while those not using the drug had an increase in bone density of
1.32 percent. These bone-loss rates are similar to that of women who are
breastfeeding or going through menopause.
- Women who were new Depo-Provera users lost bone density more rapidly
than did longer-term users.
Once the Depo-Provera users stopped getting the injections, however, they
gained a significant amount of bone density compared to non-users for the same
period. For example:
- The average amount of bone gained in a year for women who quit using
Depo-Provera was 1.34 percent at the hip, compared to a slight loss of
0.19 for women who were not taking the drug.
- Density at the spine increased 2.86 percent for women who quit the drug
compared to an increase of 1.32 percent for women who were not taking the
drug.
It’s not clear from studies to date whether other hormonal methods of
birth control might affect bone density, Scholes said. She and her colleagues
are currently conducting a study of the effect of oral contraceptive use and
discontinuation on women’s bone density.
Scholes noted that a recent U.S. Surgeon General’s report on bone health
and osteoporosis provides a number of steps that teens and young women can
take to improve or maintain bone density. The 2004 report recommends:
- Eat foods high in calcium and vitamin D
- Participate in regular weight-bearing exercise
- Don’t smoke
- Limit consumption of alcoholic beverages
Scholes’ study was funded by a grant from the National Institute of Child
Health and Human Development, National Institutes of Health. The co-authors
are Group Health investigators Andrea Z. LaCroix, PhD, Laura E. Ichikawa, MS,
and William E. Barlow, PhD, and the University of Washington School of
Medicine’s Susan M. Ott, MD.
Top
Keeping blood pressure and cholesterol low may help some dementia
patients
Could the same actions that help prevent a heart attack or stroke also
prevent or slow the memory loss, confusion and thinking problems of dementia?
A study from the University of Michigan and Group Health Center for Health Studies (CHS) suggests that for many people, the answer
could be yes.
And for some, the impact of steps such as controlling blood pressure and
cholesterol might be greater than the effect of high-priced memory-preserving
drugs.
Published in the December 15 issue of the Journal of the American
Medical Association, the study presents a comprehensive review of what’s
known—and what's not—about a condition called mixed dementia.
Mixed dementia is a combination of Alzheimer’s disease and vascular
dementia, caused in part by problems with blood flow in the brain. It may
affect as many as 20 percent of the 6.8 million Americans with dementia. It is
particularly common in older patients, who often have memory problems due to
several conditions at once.
Doctors now think that many people with symptoms attributed solely to
Alzheimer’s—memory loss, confusion, wandering, trouble following
instructions—may in fact have mixed dementia.
"Having risk factors like high blood pressure and high cholesterol
does damage to small blood vessels in the brain and can cause death of brain
cells over time," says lead author Kenneth Langa, MD, PhD, of the
University of Michigan Medical School. "In addition, the Alzheimer’s
disease process itself can affect the walls of blood vessels in the brain,
making strokes more likely. Strokes can cause dementia through the death of
large areas of brain tissue, or through the build-up of damage from multiple
small strokes cased by athero-sclerosis in small arteries in the brain or the
larger carotid arteries in the neck."
In other words, processes that hurt the cardiovascular system also hurt the
brain, and inflict a further toll on those with Alzheimer’s disease.
For the new paper, Langa and CHS director Eric B. Larson, MD, MPH, reviewed
all recent medical studies on mixed dementia, vascular dementia and Alzheimer’s.
They analyzed hundreds of articles, noting any results from drug studies that
were relevant to mixed dementia.
The review shows that drugs designed to slow the progression of Alzheimer’s
disease have about the same effect in people with mixed dementia as in people
with Alzheimer’s alone. That is, in some people they cause a measurable but
not dramatic improvement on tests of cognitive function or other measures, or
slightly slow an inevitable decline. The authors looked at drugs like
galantamine (Reminyl), rivastigmine (Exelon), donepezil (Aricept) and
memantine (Namenda).
But when the authors reviewed the evidence relating to heart-protecting
therapy and dementia, they found significant benefits. They conclude that
efforts to treat cardiovascular risk factors, especially high blood pressure,
may be more effective than memory drugs in protecting brain function.
Still, the authors note that more studies are needed to give doctors a full
picture of mixed dementia, and to show them what works, and what doesn’t, in
preventing and slowing it.
"Until then, doctors should continue talking with each patient or
family individually about the treatment that’s right for them," says
Larson. That discussion, in all patients with
dementia that might have a cardiovascular component, should include advice
about lifestyle changes and treatments to address risk factors such as high
blood pressure, high cholesterol, diabetes and physical inactivity. In
patients with heart rhythm problems, blocked neck arteries or clotting
disorders that can greatly increase the risk of stroke, further treatment may
be needed.
If a decision is made to prescribe one of the new Alzheimer’s drugs, the
authors recommend that doctors follow up with patients or their families in
two to three months, to see if there has been any improvement in memory or
behavior, or whether the patient’s cognitive decline has slowed. A
discussion of costs and benefits, because of the high monthly cost of the
drugs, is also advised.
"Mixed dementia will continue to grow in importance as our society
ages and deals with the cardiovascular effects of our current obesity and
diabetes epidemics," Langa says. "We need to help those who have it
now, and gather the data that will help us take steps to prevent it in the
future."
In addition to Langa and Larson, the study was co-authored by Norman
Foster, MD, a professor of neurology at the University of Michigan. The
study was funded by the National Institute on Aging, the Alzheimer’s
Association, the Hartford Foundation and the Paul Beeson Physician Faculty
Scholar program.
Top
Study links sexual behavior, genetic factors to increased risk of
kidney infection in women under 50
Researchers at Seattle-based Group Health Cooperative and the University of
Washington (UW) report that some of the same factors that put women at risk
for simple, lower urinary tract infections (UTIs)—as well as some unexpected
factors—also make them susceptible to more serious kidney infections.
Lead researcher Delia Scholes, PhD, senior investigator at Group Health
Center for Health Studies and colleagues found that, like
bladder infections, kidney infections in women under age 50 are linked to:
- Frequent (more than three times per week) sexual intercourse in the
previous 30 days
- A recent urinary tract infection
- A new sex partner in the previous year
- Having a mother with a history of UTIs
- Recent spermicide use
In addition, the researchers found a higher risk of kidney infection among
women with a history of incontinence and diabetes. The study appears in the
January 4 issue of the Annals of Internal Medicine.
"The incontinence finding is still a bit of a puzzle," said
Scholes. "More research will be needed to understand the type of
incontinence that is associated with kidney infections, as well as whether
incontinence typically occurred before or after the kidney infection symptoms.
The role of diabetes also warrants further study."
The study fills a gap in knowledge about a condition that affects more than
250,000 women in the United States each year. Most of what is known
about kidney infections comes from studies of older, hospitalized patients.
What the Group Health/UW study shows is that the great majority of these
infections—over 90 percent—occur in essentially healthy women who are
treated on an outpatient basis.
The study’s findings support the conventional view that kidney infections
likely follow bladder infections and thus may help doctors identify patients
at risk for kidney infections, so that they may be encouraged to follow advice
for preventing lower UTIs.
To conduct the study, the researchers interviewed 242 women, aged 18 to 49,
who had been treated for kidney infections at Group Health outpatient medical
centers. They also collected information about their treatment from
laboratory, pharmacy, enrollment, and other automated databases. Then they
compared data from these cases to data from 546 similar women with no history
of kidney infections in the previous five years.
The study was funded by a grant from the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), part of the National Institutes of
Health. The co-authors are Thomas M. Hooton, MD, Pacita L. Roberts, MS, Ann E.
Stapleton, MD, and Walter E. Stamm, MD, at the University of Washington, and
Kalpana Gupta, MD, MPH, now at Yale University.
Additional information about preventing UTIs is available online at http://kidney.niddk.nih.gov/kudiseases/pubs/uti_ez/index.htm#7
Top
People
Denise Boudreau named assistant investigator
Denise Boudreau, PhD, recently accepted the position of assistant
investigator at Group Health Center for Health Studies (CHS). Boudreau is a clinical
pharmacist who earned a doctorate in Pharmaceutical Outcomes Research and
Policy at the University of Washington in 2002. With a special interest in
the fields of pharmaco-economics and pharmaco-epidemiology, Boudreau joined
the CHS staff as a research associate in 2003. She is already working on an
impressive list of funded studies, including serving as principal
investigator on two investigations of medication and site-specific cancer
risks, as well as a study to evaluate the cost-effectiveness of measures to
improve mammographic screening.
Top
Research Highlights
An intervention that combines reducing fear of movement with increasing
physical activity showed positive results for primary-care patients with
chronic back pain, according to a Group Health study in the February
2005 issue of the journal Pain. Led by CHS senior investigator
Michael Von Korff, ScD, the study evaluated the effectiveness of an
intervention delivered by a psychologist and a physical therapist in a
four-session program. Compared to a control group, those who received the
intervention reported greater sustained reductions in pain-related fear,
average pain, and activity limitation due to back pain. CHS co-authors on
the study were Benjamin Balderson, PhD, Katie Saunders, Diana Miglioretti,
PhD, and Elizabeth Lin, MD, MPH.
Overweight and obese women who take oral contraceptives are 60 percent
to 70 percent more likely to get pregnant while on the birth-control pill
than women of lower weight, according to a study from the Fred
Hutchinson Cancer Research Center (FHCRC) and Group Health. The research,
published in the January 2005 issue of Obstetrics & Gynecology,
was led by FHCRC’s Victoria Holt, PhD, MPH, and conducted among Group
Health members. It was the largest case-control study of its kind to examine
the link between body-mass index and oral-contraceptive failure. CHS
Senior Investigator Delia Scholes, PhD, was a co-author of the study.
Top
Four gun storage practices each appear to be protective against the
risk of suicide and unintentional firearm injuries among children and
teens, according to a new study led by David Grossman, MD, MPH,
medical director of preventive care at Group Health and a CHS
investigator. These practices are: 1) keeping a gun locked; 2) keeping a
gun unloaded; 3) storing ammunition locked; and 4) storing ammunition in a
location separate from the gun. The study, conducted with Harborview
Injury Prevention and Research Center (HIPRC), is published in the
February 9, 2005 issue of the Journal of the American Medical
Association.
Adding clinical breast exams to a mammography screening program
provides only a modest benefit in detecting cancer, according to a
Group Health study published in the February 2005 issue of the American
Journal of Roentgenology. The study of 61,688 women 40 and older (574
with invasive breast cancer) who participated in Group Health’s Breast
Cancer Screening Program found that mammography plus clinical breast
examination detected 82 percent of the cancers; mammography alone detected
78 percent of the breast cancers; and clinical breast examination alone
detected 21 percent of the cancers. Thus, adding clinical breast
examination to screening mammography detected an additional 4 percent of
cancers in the study population. "Given this modest benefit and the
current lack of evidence of mortality reduction for early detection of
cancers by clinical breast exam alone, it is unlikely that the addition of
clinical breast examination to a mammography screening program will result
in substantial mortality benefits," said lead author Nina Oestreicher,
PhD, a former CHS research assistant who is now a scientist at Kaiser
Permanente Division of Research in Oakland, CA. Other researchers on the
study were CHS’ Deborah Seger and Diana Buist, PhD, and CHS affiliate
investigators Constance Lehman, MD, MPH, of Seattle Cancer Care Alliance
and Emily White, PhD, of the Fred Hutchinson Cancer Research Center.
Top
Having a breast lump is the most predictive symptom of breast cancer,
whether it is reported at a screening or diagnostic exam or in conjunction
with other symptoms, according to a Group Health study in the
November/December 2004 issue of the Journal of the American Board of
Family Practice. Led by CHS research associate Erin Aiello, MPH, the
study examined the association between self-reported symptoms (lump,
nipple discharge, pain, other) and breast cancer risk for screening and
diagnostic mammograms in more than 57,000 Group Health women. Other CHS
researchers on the study were Diana Buist, PhD, MPH, and Deborah Seger.
Emily White, PhD, an investigator at Fred Hutchinson Cancer Research
Center, and NCI’s Steve Taplin, MD, MPH, a former CHS investigator, also
contributed.
Peak rates of community-acquired pneumonia (CAP) in seniors coincide
with flu season, according to a three-year study of more than 46,000
Group Health seniors. The study, led by CHS Research Assistant Mike
Jackson, MPH, is among the first to assess rates of both hospitalization
and outpatient visits for pneumonia among community-dwelling seniors. The
researchers concluded that men are more prone to pneumonia than women.
Other risk factors include smoking, heart and lung problems, diabetes,
dementia, and taking the medication prednisone. The researchers estimate
one in 20 people aged 85 or older will have an episode of CAP each year.
Other CHS researchers on the study included Onchee Yu, MS, Christi Hanson,
and Lisa A. Jackson, MD, MPH. The work appears in the December 2004 issue
of the journal Clinical Infectious Diseases.
Increasing the number of mammograms radiologists are required to read
is unlikely to improve their overall performance, according to
research led by CHS Senior Investigator William E. Barlow, PhD. The study,
which appears in the December 15, 2004 issue of the Journal of the
National Cancer Institute, was based on surveys from 124 radiologists
and cancer outcome data from nearly half a million mammograms done at
Group Health, in New Hampshire, and in Colorado. The authors found no
association between accuracy and years of interpreting mammograms or
volume.
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