Sleep disruption and perceived nighttime hot flashes trigger mild symptoms of depression during menopause, according to a new study published in the Journal of Clinical Endocrinology & Metabolism. Using a gonadotropin-releasing hormone agonist (GnRHa) experimental model to suppress estrogen levels in 29 premenopausal women, the researchers discovered that a worsening of mood was predicted by factors such as reductions in perceived sleep efficiency (all P<.045) and the number of nighttime (P<.006) hot flashes, but not the number of daytime (P<.28) hot flashes.
"Our results indicate that bothersome daytime hot flashes are not related to menopausal depressive symptoms -- which many people believed to be the case," Hadine Joffe, MD, MSc, Director of the Women's Hormone and Aging Research Program and the Division of Women's Mental Health at Brigham and Women's Hospital and Dana Farber Cancer Institute at Harvard Medical School said.
"The findings also show that it is not just the sleep problem related to the nighttime flashes that is linked with the mood problem. Rather, both nighttime hot flashes and sleep problems are of concern." The study included 29 healthy premenopausal women, ages 18 to 45, who reported no hot flashes, sleep disorders, or psychiatric illnesses. All women received a one-time dose of intramuscular leuprolide at 3.75 mg/day to rapidly induce hypoestrogenism and maintain ovarian suppression for the study period.
Depressive symptoms (using the Montgomery Åsberg Depression Rating Scale and the Beck Depression Inventory), sleep parameters (using two ambulatory polysomnography studies), subjective sleep quality, serum estradiol, and hot flashes were assessed both at baseline and after 4 weeks. Additionally, all women used a diary to record their hot flashes twice a day over the 4-week period - once in the morning to document the nighttime hot flashes and once in the evening to document the daytime flashes. Joffe and colleagues used an experimental model, rather than a naturalistic approach, in order to precisely assess the sequence of symptom onset.
"These common menopausal 'brain' symptoms of hot flashes, sleep disturbance, and depressive symptoms often present together, and it is hard to know which came first and which problem may be contributing to the other in naturalistic studies," she explained to MedPage Today. "This approach also enables us to subtract out each women's own baseline sleep and mood patterns in order to isolate the effect of hot flashes on sleep and mood." JoAnn E. Manson, MD, DrPH, chief of preventive medicine at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, agreed that the method was successful for eliminating confounders and identifying a significant association. "Mood changes haven't been clearly linked to hot flashes or sleep quality in the past, and this study disentangles a lot of other potential contributing factors," she said.
In addition, "because the women are being compared with themselves, you don't have the potential confounding of aging or life circumstances that might contribute to symptoms in a natural menopause setting." Joffe too pointed out that "naturalistic studies are complicated by the variable amount of time that someone is symptomatic and the common co-occurrence of age-related changes in sleep that can be hard to separate out from menopause-related sleep changes." Nanette Santoro, MD, endowed chair in the Department of Obstetrics and Gynecology and professor in the Division of Reproductive Endocrinology at the University of Colorado School of Medicine in Aurora, called Joffe et al's method "an elegant approach, because it isolates the variable of estrogen and re-creates the problems that menopausal women often complain about."
And while she agreed that the study eliminated the confounding that often occurs around the time of natural menopause, she did note that "inducing 'medical menopause' with Lupron may not really mimic the same set of physiologic changes that happen in natural menopause, as the estrogen withdrawal is more rapid and perhaps more severe in this model." Joffe and colleagues concluded that women who reported having frequent nocturnal hot flashes were more likely to have mild symptoms of depression than those who reported fewer or no nocturnal hot flashes. Additionally, it was nighttime hot flashes, not those in the daytime, that were linked to depressive symptoms.
Manson said that one finding she found particularly interesting was that the subjective perception of nighttime hot flashes was more related to depressive symptoms than hot flashes that were objectively measured: "If women were not aware of being awakened by [the hot flashes], it may be less of a risk factor for depressive symptoms." One of the biggest takeaways from the results, the researchers said, was the importance of screening for mood disturbances during the menopausal transition and early menopause. "This [study] provides specific information to women and clinicians about the importance of treating nighttime hot flashes/night sweats as part of the approach to improving mood disturbance in this population," Joffe said. Manson agreed that the results suggest that clinicians should ask patients about nighttime hot flashes since they may be an important contributor to sleep disruption and to the development of depressive symptoms.
Joffe said that the small number of participants -- something often viewed as a limitation -- was actually one of the study's key advantages because "the variability is reduced since you can subtract each woman's own baseline profile and look at changes within each person." Another expert asked for her opinion, Diana L. Bitner, MD, NCMP, director of the Women's Health Network at Spectrum Health in Grand Rapids, Mich., said she agreed that the small study made sense: "[Joffe] was looking at each patient as their own control, done purposefully with the intent of understanding the evolution of symptoms as estrogen drops -- which allows for a smaller sample size."
Santoro also commented that the number of participants was well balanced against the extremely detailed nature of the study design. "The use of polysomnography and all the rating scales used, along with the multiple hormone assessments would be very, very difficult to do in a large sample. A larger sample with less detailed assessments might not necessarily be more convincing." Manson said that moving forward, further research is warranted, and ideally with a larger study. "One of the next types of studies to be done are what treatments are most effective in reducing hot flashes and improving sleep quality," she said. "It could look at the comparative effects of hormonal and nonhormonal therapies on nighttime hot flashes and poor sleep quality, as well as the depressive symptoms."
Women who experienced a steeper decline in estrogen levels prior to menstruation were more likely to experience migraines, researchers found. In an analysis of data collected as part of the long-term longitudinal Study of Women's Health Across the Nation (SWAN), migraineurs' conjugated urinary estrogens (E1c) declined in the 2 days before luteal peak at a faster absolute rate than nonmigraineurs (33.8 pg/mgCr vs 23.1 pg/mgCr, P=0.0002) and at a higher percent change than nonmigraineurs (40% versus 30%, P=0.001), Jelena Pavlovic, MD, PhD, of the Albert Einstein College of Medicine in New York City, and colleagues reported in Neurology. The study authors did not find significant differences in the groups when they looked at absolute peak and daily hormone values, and they found no significant differences in the the periovulatory phase.
As part of a secondary analysis within the migraineurs' group, the study authors determined that hormone patterns were similar regardless of whether the woman had a migraine that cycle. As a result, Pavlovic and her team formed a "two-hit" hypothesis in which women with rapid estrogen level dips before menstruation are more sensitive to migraine triggers, such as stress, lack of sleep or a glass of wine. It's a combination of the estrogen drop and the additional trigger that result in a migraine. Joel Saper, MD, of the Michigan Headache & Neurological Institute in Ann Arbor, who was not involved in the study, likened the hormonal changes in Pavlovic's hypothesis to a loaded gun. "The rate of fall might sort of load the gun but some other factor has to trigger it," he said.
"If our two-hit hypothesis is valid, woman can intuitively recognize that 'this is a bad time for me' and realize they need to take a break," Pavlovic said, explaining that the two 2 before and 3 days after a woman begins bleeding are the times she is most likely to have what's referred to as a menstrual migraine. The study included 114 migraineurs and 223 controls from SWAN's Daily Hormone Study (DHS), in which participants collected their first morning urine for an entire menstrual cycle or 50 days and completed daily symptom diaries, including headaches. Pavlovic and her colleagues excluded women who reported headaches but were not diagnosed with migraines to avoid including patients with undiagnosed migraines in the control group. "Most studies of migraines had been done in different subtypes of women in the migraine group itself," Pavlovic said, explaining that migraine studies that included controls were few and small. "I wanted to compare migraineurs to controls." Study participants' average age was 46.9, but Pavlovic said that was because there were a few older women in the group that pushed the average up. Most of the patients were 42 or 43. Most were perimenopausal, according to the study.
SWAN participants are on the older end of menstruating women, which is a limitation of the study, but Pavlovic said several factors mean the result should stand in for all menstruating women: her team only included at daily urine and symptom data for the first and therefore youngest cycle; and two SWAN endocrinologists confirmed that each woman was indeed having a true ovulation cycle. "The quality of this data is unprecedented," Pavlovic said, praising the SWAN researchers.Although migraineurs in the study didn't necessarily meet the diagnostic criteria laid out in the International Classification of Headache Disorders (ICHD), Pavlovic said the fact that SWAN participants were asked whether they'd been told by a healthcare provider that they have migraines is sufficient because migraines are "tremendously" underdiagnosed. The control group had a higher proportion of Chinese and Japanese participants than the migraineur group, which is a limitation of the study.
Saper said the study is well-designed but not particularly surprising because headache specialists have long known that migraines were linked to estrogen levels before menstruation. However, he said, the work of Pavlovic and her team demonstrates an objective difference between migraineurs and controls: the rapid rate of estrogen decline. "I think it re-emphasizes the importance of a woman's biological changes around the menstrual period and that migraine for women are neuroendocrinically different," said Saper. "They are not the same as women who don't have migraines around their menstrual period and maybe well beyond it. "In the future, Pavlovic would like to further study hormone level differences between migraineurs and controls on a more granular level and see how oral contraceptive pills affect migraineurs.
The tool kit is available electronically at www.immunizationforwomen.org/toolkit/flu. You can also visit ACOG's Immunization for Women website, www.immunizationforwomen.org, for additional info and resources for providers and patients. The website has two sections,
one for ob-gyns and other health care providers, and one for patients.
Current asthma prevalence among obese women in the U.S. is almost double that of normal-weight women, but the same association was not seen in men, according to a CDC report. In 2011–2014, obese women had a 14.6% prevalence for asthma versus 7.9% for normal-weight women and 9.1% for overweight women, reported Lara Akinbami, MD, of the National Center for Health Statistics (NCHS) in Atlanta, and colleagues.
Current asthma prevalence did not differ significantly by weight status for men, they wrote in an NCHS Data Brief. They group analyzed 2001-2014 data from the National Health and Nutrition Examination Survey (NHANES) across all adult age groups, and found that obesity was significantly associated with higher asthma prevalence. "This pattern was consistent across most demographic subgroups, except among men, for whom no statistically significant difference in current asthma prevalence by weight status was observed," they wrote.
While the current report bolsters findings from previous studies suggesting that obesity is a strong risk factor for asthma in adult women, but not men, the reasons for this are not clear, Akinbami said. "Interestingly, asthma prevalence is higher in young boys than young girls, but this switches around the time of puberty. In adults, asthma prevalence is higher in women than men," she said. It has been suggested that sex-related differences in fat distribution may at least partly explain the largely gender-specific asthma risk associated with obesity, and that hormones secreted by ectopic fat may contribute to asthma.
"My feeling is that it is the aggregation of a number of risk factors that contribute to the higher asthma risk among obese women," commented Erwin Gelfand, MD, of the National Jewish Health in Denver. "Animal studies, and some human studies, have suggested that hormonal changes related to estrogen, leptin or other hormones may play a role in asthma," said Gelfand, who was not involved in the research. Obesity was officially recognized as a major risk factor for asthma in adults by the American Thoracic Society in a 2010 report, which noted that obesity-related asthma is most likely a distinct phenotype of the chronic lung disease, characterized by increased severity and poor response to treatment.
Akinbami and colleagues found that from 2011 through 2014, the overall prevalence of asthma among adults in the U.S. was 8.8%, with 11.1% of obese adults, 7.8% of overweight adults, and 7.1% of normal-weight adults having asthma. Also, obesity was associated with higher asthma prevalence rates among all age groups and racial groups. Overall asthma prevalence increased from 2001-2002 (7.1%) to 2013-2014 (9.2%). Prevalence rates increased during this time period among overweight adults, but not among adults who were obese or whose weight was normal. "That was not what we expected to see," Akinbami said. "Over the entire period, obese adults had the highest prevalence of asthma, but that prevalence rate did not increase."
he prevalence of current asthma among obese non-Hispanic whites was 10.9%, compared with 8.1% among normal-weight white adults, while the prevalence among non-Hispanic black adults who were obese was 13.6% compared with 6.6% in normal-weight blacks. Obese Hispanic adults had an asthma prevalence of 9.6% versus 5.7% among normal-weight Hispanics. No significant differences in asthma prevalence rates were seen between normal-weight and overweight adults within any racial group. For all age groups, current asthma prevalence was highest among adults with obesity, and no significant difference in asthma prevalence was seen between those in the normal weight and overweight categories.
"There was an increasing trend in asthma prevalence as weight increased that was observed most clearly in the 60 and over age group," the researchers wrote. Akinbami noted that further research is needed to determine if weight loss is an effective treatment for asthma in patients who are also obese. "We might be able to lower asthma rates by reducing obesity, but that is really an open question at this point," she said.
A vaginal ring that elutes dapivirine, an investigational antiretroviral drug, over a 30-day period appeared to prevent HIV infection in sexually active women, but its effectiveness was dependent upon women actually using the ring, researchers reported. In the ASPIRE trial, the incidence of HIV-1 infection in the dapivirine group was 27% lower (95% CI 1-46, P=0.05) than in the placebo group, reported Jared Baeten, MD, of the University of Washington in Seattle, and colleagues in the New England Journal of Medicine. However, in post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 (56%, 95% CI 31-71, P<0.001) but not among women age 21 or younger (−27%, 95% CI −133 to 31, P=0.45).
In the second trial, HIV risk was reduced by 31% overall, and by 37% among participants older than 21, said Annalene Nel, MBChB, PhD, of the International Partnership for Microbicides (IPM), which developed the monthly dapivirine ring.Both studies were presented at the Conference on Retroviruses and Opportunistic Infection (CROI). The device is a silicone elastomer vaginal matrix ring containing 25 mg of dapivirine. "Now, for the first time, we have two trials demonstrating that a female-controlled HIV prevention method can safely help reduce new HIV infections," Baeten said at a CROI press conference. "I'm optimistic about what these results might mean for women worldwide."
The American Cancer Society published new mammography screening guidelines in the Journal of the American Medical Association.
The new key recommendations for women at average risk are:
These guidelines now fall between the recommendations of the U.S. Preventive Services Task Force (routine screening starting at age 50, and optional earlier) and the American College of Radiology and some other groups that recommend annual screening beginning at age 40.
An FDA advisory committee voted 18-6 to recommend approval for flibanserin, a drug meant to treat sexual dysfunction and loss of sexual desire in women.
The "yes" vote at the joint meeting of the Bone, Reproductive and
Urologic Drugs Advisory Committee and the Drug Safety and Risk
Management Advisory Committee included a requirement for "certain risk
management options beyond labeling," such as provider certification and
Flibanserin, a product of Sprout Pharmaceuticals, is proposed for
hypoactive sexual desire disorder (HSDD) in premenopausal women. The
suggested dose is a 100-mg tablet taken in the evening before bed.
for Disease Control and Prevention (CDC) has declared a flu (influenza) epidemic
in the United States. There has been antigenic drift in one
of the strains of the virus seen circulating now versus the strain chosen for
the vaccine. Therefore, it is extremely important for providers to promptly
treat all patients with influenza-like-illness (ILI), even women who have been vaccinated.
To date there have been 21
pediatric deaths and more than double the number of hospitalizations from the
previous flu season. So far, among the
35 hospitalized women of childbearing age (15-44 years), 12 (34.3%) were
pregnant. ACOG and CDC
recommend everyone 6 months and older receive a flu shot each year. Vaccination
is particularly important for pregnant women who are at higher risk of
complications and severe illness from influenza.
IMPORTANT: If any of your pregnant patients
present with influenza-like-illness (ILI) such as fever >37.8°C (100.0°F), cough or sore
throat, chills, body aches/muscle pain, headache begin treatment with antivirals immediately. Your
decision should be based on clinical assessment and you should not wait nor rely on rapid test results which are often
inaccurate. Patient with influenza-like illness should be treated with
antiviral medications presumptively regardless
of vaccination status.
strain of this year’s vaccine is not a good match, the vaccine can still
protect against other strains of the virus and vaccination is still the best form of prevention.
information please visit ACOG’s Immunization for Women website.
Click Here to download the Influenza Season Assessment Algorithm.
Obese women with estrogen receptor-positive breast cancer had a 52%
lower risk of recurrence when they regularly used aspirin or other
nonsteroidal anti-inflammatory drugs (NSAIDs), a review of patient
records showed. NSAID users had more than a 2-year delay in the
time to recurrence as compared with obese breast cancer patients not
reporting regular NSAID use. Laboratory studies of breast cancer
cell lines provided evidence suggesting that obesity stimulates
production of estradiol and aromatase - which might be inhibited, at
least in part, by NSAIDs, as reported online in Cancer Research.
Recent use of some oral contraceptives is associated with an increased risk of breast cancer, researchers reported. In
a nested case-control study, women who had used birth control pills
within the previous year had a 50% increase in the risk of disease,
compared with those who had never or formerly used the drugs, according
to Elisabeth Beaber, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues. But
the risk varied with formulation of the contraceptives; some types -
notably those with low-dose estrogen - were not associated with
cancer, Beaber and colleagues reported in the Aug. 1 issue of Cancer Research.
Many women ask about oral contraceptives and breast cancer," and the
benefits and risks need to be clearly understood, commented Holly Pederson, MD, of the Cleveland Clinic. In women under 50 "their absolute risk of breast cancer is less than 2%." But
while that risk "raises red flags," the main concern is not oral
contraceptives, she said, but familial and genetic predispositions, such
as mutations in the BRCA genes. Those factors, she noted, were not analyzed in the study. Pederson
added that it's "important to reinforce to our patients that the most
commonly used birth control pill - low-dose [estrogen] monophasic -
was even in this study not associated with an increased risk."
The FDA has approved a molecular test for human papillomavirus (HPV)
DNA as a first-line, stand-alone screen for cervical cancer. The
agency approved the cobas HPV test to screen women ≥25 for infection
with 14 high-risk HPV strains, including HPV 16 and 18, which account
for most cases of cervical cancer in the U.S. and worldwide. The approval follows a unanimous recommendation
from an FDA advisory committee that reviewed evidence on test results
presented by FDA staff and by the test manufacturer, Roche Molecular
"Today's approval offers women and physicians a new
option for cervical cancer screening," Alberto Gutierrez, PhD, of the
FDA Center for Devices and Radiological Health, said in a statement.
"Roche Diagnostics conducted a well-designed study that provided the
FDA with a reasonable assurance of the safety and effectiveness when
used as a primary screening tool for cervical cancer."
initially approved the molecular test in 2011 for use in conjunction
with or as a follow-up to a Pap test. The new approval gives healthcare
professionals the option to use the HPV test alone or as a co-test with
cervical cytology (Pap). According to the FDA, women who test
positive for HPV 16 or 18 should proceed directly to colposcopy. A
positive test for one or more of the other 12 high-risk HPV strains
should be followed by a Pap test to determine the need for colposcopy.
An FDA advisory committee voted unanimously Wednesday to recommend
that the Pap smear be replaced with a human papillomavirus (HPV) test as
the first-line standard of care for cancer screening. The FDA's
Medical Devices Advisory Committee Microbiology Panel agreed by a vote
of 13-0 in each of three successive votes that the cobas viral DNA test
for HPV - made by Roche Molecular Systems - was safe and effective
for cervical cancer screening, and that the benefits of the tests
outweighed the risks.
The cobas test currently has approval as a follow-up assessment for
women 21 and older who have abnormal Pap tests, and as a co-test with
the Pap smear to screen for the high-risk p16 and p18 HPV strains in
women 30 to 65. The test comprises genotyping for HPV16 and 18 and
pooled assessment of 12 additional high-risk HPV strains. According
to the proposal submitted by Roche, women 25 and older who test
positive for HPV16 or 18 would proceed directly to colposcopy for
further assessment. Patients who test negative for HPV16 or 18 but
positive for the other high-risk strains would have a Pap test to
determine the need for colposcopy. Women who have a completely negative
test would be followed at their physician's discretion.
New guidance from the American Heart Association/American Stroke Association
focuses on stroke prevention specifically in women, who have a risk
profile that differs from that of men.
Many stroke risk factors are shared by both men and women, so the new
document zeroes in on those that are unique to women, including issues
surrounding pregnancy, oral contraceptive use, and postmenopausal hormone use,
and those that have a greater impact in women, including migraine with aura,
diabetes, hypertension, obesity, metabolic syndrome, and atrial fibrillation.
The new AHA/ACC guidance was written by a group chaired by Cheryl Bushnell, MD, MHS, of Wake Forest Baptist Medical Center in Winston-Salem, N.C., and published online in Stroke: Journal of the American Heart Association. "It
is very important that there is a specific stroke prevention guideline
for women because we're not the same as 50% of the population," Dolora Wisco, MD, a neurologist at the Cleveland Clinic, said. "We have our own risk factors on top of the ones that are commonly seen out there."
Women are disproportionately affected by stroke; of an estimated 6.8
million people living in the U.S. after surviving a stroke, 3.8 million
are women. In addition, stroke is the fifth leading cause of death for
men, but third for women. "These basic facts about the epidemiology of disease are not well known to the general public," commented James Meschia, MD,
a vascular neurologist at the Mayo Clinic in Jacksonville, Fla. "It is
important to heighten awareness of risk in women so that greater
attention [is] placed on lowering risk."
This guidance document is the first stroke prevention guidance
specifically geared toward women, and it goes into greater depth about
the issues surrounding stroke in women than previous documents that
included both sexes. After discussing the current evidence and areas
where research is lacking, the authors made recommendations related to
pre-eclampsia, hypertension during and after pregnancy, central venous
thrombosis, oral contraceptives, menopause, hormone replacement, and the
risk factors that affect women more than men. Two of the more
noteworthy recommendations, according to Wisco, are those dealing with
the prevention of pre-eclampsia with low-dose aspirin in women with
chronic primary or secondary hypertension or previous pregnancy-related
hypertension, and with calcium supplementation for women with a low
dietary intake of the nutrient to prevent pre-eclampsia.
"Women usually are not ... put on aspirin during pregnancy or at
younger age," she said. "So this is a bit of a different take on
prevention of stroke."Another noteworthy recommendation was the
one calling for blood pressure measurement before the start of hormonal
contraception, according to Meschia. "I am not sure that every
clinician who prescribes hormonal contraception is as vigilant as can be
about this," he said. "When prescribing drugs for a younger female
population, stroke risk factor management is not always top of mind."
For Anjail Sharrief, MD,
a neurologist at Memorial Hermann-Texas Medical Center and UTHealth
Medical School, the call for a female-specific stroke risk score stood
out. "Because of the differential impact of risk factors in women,
including hormonal and pregnancy-related factors that change over the
life course, a risk prediction model that considers these factors may
allow a more accurate estimation of stroke risk for women," she said. The
guidance was endorsed by the Association of Neurological Surgeons and
Congress of Neurological Surgeons. The American Academy of Neurology
"affirms the value of this guideline as an educational tool for
neurologists," according to the document.
In 2009, the US Preventive Services Task Force
created guidelines recommending biennial mammography screening for women
between the ages of 50 and 74. And now, scientists suggest that following this
guideline would be equally effective and save the US health care system $4.3
billion a year.
The researchers, led by Dr. Laura J. Esserman, professor of
surgery and radiology at the
University of California-San Francisco (UCSF), also support other aspects of
the US Preventive Services Task Force (USPSTF) guidelines, which recommend
women between the ages of 40 and 49 are screened according to other risk
factors and women over 75 are screened depending on presence or absence of
The team says around 70% of women in the US were screened
for breast cancer in
2010, costing around $7.8 billion.
While some women are screened annually, some are screened biennially and others are screened on an "irregular basis."
Published in the journal Annals of Internal Medicine, the study employs three possible screening strategies with simulated models:
The team found that the largest factors for cost were screening
frequency, percentage of women screened, cost of mammography, percentage of
women screened with digital mammography and percentage of mammography recalls.
Dr. Esserman notes that the "USPSTF guidelines are
based on the best scientific evidence to date," adding that we need
"a better way to assess breast cancer risk and implement a more risk-based
approach to screening."
The topic of reducing screening appointments has understandably been a
controversial one. However, the researchers note that apart from
high-risk groups, less frequent screening has been proven as effective,
which is why they wanted to look into the cost differences between
Dr. Esserman says that "annual screening is associated with a greater
likelihood of false positive results, which have an adverse impact on
women's well-being and quality of life."
"From the viewpoint of women's health," she adds, "the USPSTF screening recommendations make sense."
Dr. Cristina O'Donoghue, now from the University of Illinois-Chicago,
but who was with UCSF during the study, says the billions saved could be
used toward women's health:
"We could increase women's participation in screening, improve routine
assessment of breast cancer risk and referral services for women at high
risk, offer better genetic counseling for women with a family history
of breast cancer and work on improving the quality of screening, with an
emphasis on higher-quality mammography read by specialized
In a linked editorial to the study, Drs. Joann G. Elmore and Cary P.
Gross, from the University of Washington and Yale School of Medicine,
applaud the study authors for "meticulously assessing the total cost of
breast cancer screening in the US."
They add that though "there is often cause to be skeptical about
simulation models because results are based on numerous assumptions,"
they found the study "to be reasonable and conservative."
However, they point out a few topics not covered by the study:
"Beneficial patient-centered issues, such as the reassurance women feel
after being screened, the early detection of lesions that allows for
more treatment options, and the potential to save lives, are beyond the
scope of the accompanying economic modeling study. However, they should
Drs. Elmore and Gross emphasize that other countries do not screen women
annually, such as the UK, which invites women to be screened every 3
years, starting at 50 years of age.
"Women and their providers do not know the costs associated with breast
cancer screening," they add, "and national organizations have been
hesitant to discuss this issue."
One pharmaceutical company can now brag about a nonhormonal option to treat hot flashes during menopause.Noven
Therapeutics knows that's welcome news to scores of women who've
developed a fear of hormone therapy following the increased risk of
heart disease and breast cancer seen in the Women's Health Initiative (WHI).
But Brisdelle is just an old medication dressed up in a new feminine
name and packaging – it's the antidepressant paroxetine, better known by
its brand name, Paxil."Some women won't even know it is an antidepressant," says Diana Zuckerman, PhD,
president of the National Center for Women & Families, a women's
health advocacy group, explaining that few may look at the generic name,
and of those who do, paroxetine will be much less recognizable than
The FDA has approved the combination agent Duavee to treat hot flashes and prevent osteoporosis in menopausal women. The
drug pairs conjugated estrogens with the selective estrogen receptor
modulator (SERM) bazedoxifene, with the latter replacing the progestin
that protects against the potentially increased risk of uterine
hyperplasia seen with estrogen therapy. It is indicated for women
who still have a uterus, and will come with the same boxed warning that
appears on other approved estrogen products, according to the FDA.
For women with menopausal symptoms, not all oral hormone therapy is created equal. In
a case-control study, conjugated equine estrogens (CEEs) were
associated with about twice the risk of venous thrombosis compared with
estradiol, according to Nicholas Smith, PhD, of the University of Washington in Seattle, and colleagues. The
CEEs also appeared to be associated with an increased risk of heart
attack, but the link fell short of statistical significance, Smith and
colleagues reported online in JAMA Internal Medicine.
The investigators also reported that there was no association with
stroke risk in the Heart and Vascular Health Study, which is looking at
cardiovascular events among people who are members of Group Health
Cooperative, a large health maintenance organization in Washington. The
difference between the two therapies, the investigators noted, is that
CEEs are extracted from the urine of pregnant mares and contain several
active estrogen compounds, while estradiol contains only synthetic
estradiol-17β. The study is a reminder to doctors to raise the issue of risk with patients thinking of hormone therapy, commented Diana Bitner, MD, of Spectrum Health Medical Group in Grand Rapids, Mich. "As clinicians, we need to have a personal discussion ... between the provider and the patient," she said.
For this analysis, the researchers looked for cases of venous
thrombosis, myocardial infarction (MI), or stroke among menopausal women
taking oral hormones after Jan. 1, 2003. That's about 6 months after the landmark publication of the findings of the Women's Health Initiative study, which changed the landscape of hormone therapy. That study, comparing hormone therapy with placebo, found that hormone therapy increased risks for a range of adverse events. The
new study by Smith and colleagues "adds a new wrinkle" by comparing
estrogen drugs among users, rather than between users and nonusers,
Smith and colleagues found 183 cardiovascular events among women
taking either CEES or estradiol, including 68 venous thromboses, 67 MIs,
and 48 ischemic strokes. For comparison, they included 201 matched controls who were also on hormone therapy. Analysis showed that using oral CEEs, compared with oral estradiol, was associated with:
findings of this comparative safety investigation need replication,"
they concluded, but if they were confirmed would "provide valuable
information to women and their healthcare professionals." Smith
and colleagues cautioned that unmeasured factors might have confounded
the results. They also noted that the findings only deal with active use
of hormones and say nothing about the relative risk of starting hormone
More than two-thirds of breast cancer deaths occurred in younger
women with no history of mammography or with intervals of 2 years or
more between mammograms, a study of 7,300 breast cancer patients showed. Mammographically
unscreened women accounted for 71% of breast cancer deaths over an
18-year period. Median age at diagnosis of fatal breast cancer was 49,
as compared with 72 for women who died of other causes. The
findings support initiation of mammographic screening before age 50,
Blake Cady, MD, of Massachusetts General Hospital in Boston, and
coauthors reported online in Cancer.
"Even with effective adjuvant therapies, the best method for women to
avoid death from breast cancer is to participate in regular mammography
screening," the authors concluded. "Regular screening increases the
likelihood of detecting nonpalpable cancers, and annual screening
further increases the likelihood relative to biennial screening."
detecting and treating breast cancer in younger women to prevent death
may further increase the disease-free life years saved," they added.
"Our findings suggest decreasing the intensity of efforts to screen
women older than 69 years while concomitantly emphasizing efforts to
screening young women in particular."
Breast cancer screening by mammography has a controversial history.
Studies have shown that early detection of breast cancer reduces the
risk of fatal breast cancer. However, the optimal age to initiate
screening and the interval between screens have remained unresolved. The controversy gained momentum in 2009 when the United States Preventive Services Task Force
(USPSTF) recommended that routine screening mammography begin at 50 and
that screening should be optional for younger women. The USPSTF also
suggested biennial screening, rather than annual, as an option for
average-risk women. The USPSTF position drew criticism from the
American Cancer Society, American College of Radiology, and other
organizations with a stake in breast cancer diagnosis and management. In
general, critics supported annual screening and initiation of screening
at a younger age.
Most randomized trials of screening mammography have shown that women
offered mammography have significantly lower breast cancer mortality
than do women who are not offered mammography. Results of those trials
have formed the basis of clinical recommendations. However,
randomized trials underestimate the effectiveness of screening
mammography because of their focus on women who are offered mammography
instead of women who are actually screened, the authors stated in their
introduction. Consequently, the recommendations do not reflect the
survival benefit demonstrated by long-term follow-up of patients who
undergo screening.To determine the survival benefit of women who
have been screened, Cady and colleagues analyzed data on 7,703 patients
who had newly diagnosed breast cancer during 1991 to 1999. Follow-up
continued to 2007.
The authors also examined duration of screening interval, defining
biennial screening as intervals of no more than 2 years. Women whose
most recent screen occurred more than 2 years in the past were included
in the unscreened group. The data included demographics, use of
mammography, surgical and pathology reports, disease recurrence, and
death. Investigators designated mammograms as screening or diagnostic on
the basis of absence or presence of signs and symptoms of breast
cancer. The authors determined that 1,705 of 7,703 women died
during follow-up, including 609 breast cancer deaths. Analysis of breast
cancer deaths by screening status showed that screen-detected tumors
accounted for 118 deaths, most of which (111) involved women whose
tumors were detected after two screening mammograms that occurred no
more than 2 years apart.
Additionally, 60 deaths resulted from "interval cancers," defined as
tumors that occurred in women who had at least one negative mammogram
performed no more than 2 years previously. Unscreened women
accounted for 395 breast cancer deaths. An additional 36 deaths involved
"off-program" women, defined as patients who had a history of
mammography but who had not been screened in more than 2 years. Overall,
interval cancers accounted for 34% of breast cancer deaths in screened
women, but investigators found an inverse relationship between age at
diagnosis and the proportion of deaths attributable to interval cancers.
Among women younger than 40 at diagnosis, 60% of deaths involved
interval cancers, declining to 47% among women 40 to 49, 28% in women 50
to 59, 26% in women 60 to 69, and 24% in women 70 or older.
Investigators also analyzed breast cancer and nonbreast cancer deaths
by age. Half of all breast cancer deaths occurred in women younger than
50 and 69% before age 60. In contrast, 83% of nonbreast cancer deaths
occurred in women older than 60. The data speak to the controversy about
whether screening mammography should begin at age 50 or earlier. The
results are consistent with much of the literature showing that
screening mammography lowers the stage at cancer detection, said Clifford Hudis, MD,
president of the American Society of Clinical Oncology. Earlier stage,
smaller tumors, and lower nodal involvement are all associated with
improved outcomes in breast cancer. "Some would argue that cancers
are cancers, and whether they are detected early or late, the outcome
is the same," said Hudis of Memorial Sloan-Kettering Cancer Center in New
York City. "This study suggests that is not true, that the stage really matters, even if you have changed the stage at detection. This
provides a little more support for the routine use of mammography,
which is important because of the ongoing circular debates about
screening," he said.
Accelerated partial breast irradiation (APBI) matched long-term
disease control and survival with whole-breast irradiation (WBI),
according to 10-year follow-up data from a matched-pair analysis.Rates
of local and regional recurrence were identical at 10 years. Distant
metastasis occurred less often with WBI (3% versus 6%), whereas
contralateral recurrence was more frequent with WBI (9% versus 3%),
reported Jessica Wobb, MD, of Beaumont Cancer Institute in Royal Oak,
Mich., at the Breast Cancer Symposium.
Disease-free survival, disease-specific survival, and overall
survival did not differ significantly between groups, but were
consistently higher in WBI-treated patients, Wobb added. "These
data represent one of the only ABPI series with prolonged follow-up and
show similar outcomes in a matched group of patients undergoing WBI or
APBI," Wobb concluded in a poster presentation. The findings could represent a case of too little, too late, according to invited discussant David E. Wazer, MD, of Tufts Medical Center in Boston. He reviewed data from the National Cancer Data Base,
showing a downturn in the use of brachytherapy after breast-conserving
surgery since 2008 and no substantive increase in the use of other forms
of APBI going back almost 10 years.
"Why is this happening?" Wazer asked. "I think it is because of
toxicity concerns [with APBI], the emergence of alternative short-course
hypofractionated whole-breast regimens, and the rise of single-fraction
intraoperative radiotherapy. "The emergence of breast-conserving
surgery for early-stage breast cancer has been accompanied by the
introduction of APBI as an alternative to WBI. As compared with WBI,
APBI protocols historically have required less time to complete,
offering potentially attractive quality-of-life considerations for
patients and providers. Whether the advantages of APBI came at a
cost of cancer outcomes has remained a topic of discussion. Few studies
have accumulated long-term data to compare outcomes with APBI and WBI.
Wobb and colleagues presented data from long-term follow-up of 3,009
patients treated with breast conservation at Beaumont from 1980 to 2012.
The study population comprised 2,528 women who underwent WBI after
surgery and 481 who received catheter- or balloon-based APBI. A
matched-pair analysis was performed, including age, cancer stage, and
estrogen-receptor (ER) status.The analysis included 548 of the
3,009 patients. Follow-up averaged 8 years overall but was slightly
longer in the WBI group (8.1 versus 7.8 years, P<0.001).
Mean tumor size did not differ significantly but was smaller in the APBI
group (11.4 versus 13.0 mm). T-stage, ER status, and final surgical
margins did not differ significantly between groups. Nodal involvement
was more common in the WBI group (14% versus 9%, P=0.07). Use of adjuvant hormonal therapy was significantly more common in the WBI group (68% versus 54%, P=0.001).
Comparison of 10-year clinical outcomes with APBI versus WBI produced
the following results, none of which achieved statistical significance:
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