A recently published meta-analysis* by Joseph Wax and others in the American Journal of Obstetrics and Gynecology has caused quite a stir, primarily because of the authors’ conclusion that “Less medical intervention during planned home birth is associated with a tripling of the neonatal mortality rate.” As we’ll see, things aren’t quite so simple on a closer look.

Upon reading the Wax paper, my first response was “Great, I’m going to have to read every one of the original studies to make heads or tails of this.” This is because, as Amy Romano points out when she notes the absence of forest plots (which would provide more detail on the findings of each included study, and are common among this type of paper), the meta-analysis itself is not terribly detailed* with regards to the characteristics and findings of each included study.

Likewise, it was difficult (for me anyway, perhaps someone else can chime in) to make some of the numbers add up, such as the size of the planned home birth population analyzed for neonatal deaths, and here again I feel the need to revisit each of the original studies in order to better understand the possible meaning for home birth safety.

First, the authors emphasize the conclusion that less frequent intervention is “associated with” increased neonatal death. The term “associated with” implies a statistical relationship between the two factors, but as we read further we find that other variables (such as attendant type) may play a role.

As far as I can tell, the authors did not attempt to do any calculations that would specifically tie the neonatal death rate to the decreased rate of interventions (more on this in a minute), they just find that both occurred. It may be the case that some of the neonatal deaths could have been prevented in the presence of additional interventions, but this is difficult to determine based on the paper at hand.

I also would have liked to have seen more thorough explanation of what the contrast between the perinatal deaths and the neonatal deaths might mean. Perinatal death (for which the authors report no significant difference between planned home and hospital births) is defined by the authors as stillbirth of at least 20 weeks gestation or 500g through death of a live born infant up to 28 days after birth. Neonatal death (which the author reports as elevated in the planned home birth group) is defined as death up to 28 days after delivery.

So, the elevated risk of death is among live born infants up to 28 days after delivery, but it’s hard to tell how many deaths occurred during labor/delivery or in the first few days after birth (for which we might assume a more important role for intrapartum care, such as a failure to note distress or a failure to resuscitate) versus how many occurred later, or their causes or possible prevention strategies.

Without seeing more data from the original studies on the causes and time frames of the deaths, it’s difficult to fully understand any possible implications of this finding.

The authors do say in the “Comment” section (not where you’d normally expect to find results) that “planned home births were characterized by a greater proportion of deaths attributed to respiratory distress and failed resuscitation” and refer to some of the included studies for support, but I would love to see some data extracted and presented more clearly in the meta-analysis. There were very small numbers of neonatal deaths in the referenced studies, and it’s not clear from spot-checking a couple of the original papers whether those researchers actually attributed the deaths to a lack of intervention without other confounding factors.

I’m also not entirely sure how useful it is to do a meta-analysis on home vs. hospital birth using data from lots of (Western) countries when the mostly non-U.S. countries have a range of current practices/trends in home birth and midwifery (such as different standards for midwifery education and stronger traditions of home birth, etc.), and rather different healthcare systems.

I recognize that this is going to be an issue for other meta-analyses on birth topics, and I’d be interested in being pointed to any good discussions of this particular issue or in hearing others’ take in the comments.

The authors raise one other issue related to the neonatal death rate that is different from the “less intervention” conclusion — they note that when the analysis excluded studies in which the providers were not “certified or certified nurse midwives,” the odds ratios for all neonatal death and “nonanomalous” (without congenital issues) neonatal death became non-significant.

In other words, when the planned home births had some type of certified midwife present, the neonatal death rate was no different than that in the planned hospital birth group. Readers, however, must have access to the full text of the article in order to view this conclusion, which is not emphasized in the abstract or media coverage of the paper.

The authors do not provide much further definition or discussion of the attendant issue, leaving us without (again, without rereading each paper) a clear understanding of whether the neonatal deaths might have occurred in unattended/unplanned home births and/or births with some other form of attendant, or how the rate of interventions varied by type of attendant.

The Pang study, for example, contributed a large chunk of the population analyzed for neonatal deaths, but has been widely debated and criticized for including unplanned home births in its analysis of neonatal death at home birth, so further review of the methods of each study may be warranted.

The authors chose to clearly associate low rates of intervention with neonatal death, but I wonder if they would also be willing to support a statement that “lower rates of medical intervention during planned home birth is not associated with increased neonatal mortality when attended by a certified or certified nurse midwife.”

There is possibly a discussion to be had about whether different types of non-certified attendants (especially those cases with unattended or unplanned home births) had all of the sometimes necessary interventions and techniques at their disposal, but the Wax analysis does not attempt to delve into this issue.

There is some discussion of the inclusion of unplanned home births in a letter from Janssen and Klein and a reply letter from Wax, for those who have access to the journal. In the reply, Wax stands by the conclusions based on their exclusion of premature births (which they expect will reduce the number of included unplanned home births), but also notes that “In addition, the purpose of our article, as clearly stated, was to evaluate morbidity, not mortality.” Mortality, however, seems to be the prime area of interest in and focus on the article, and is a clear point of emphasis in the authors’ abstract.

Ultimately, I don’t think this meta-analysis would have warranted much attention at all if it were not for the authors’ bold statement of association between decreased rates of intervention at home birth and tripled odds of neonatal death. Without that bit of provocation through the authors’ framing (and relative lack of emphasis on the difference having a midwife attendant made, or the low absolute risk of neonatal death), I don’t think most readers would have thought much of this paper or considered it to make much of an impact on knowledge in the field.

Given the small number of included studies, readers interested in better understanding safety data on home birth are probably better off getting copies of the papers Wax refers to in the analysis, and looking at each one for its relevance.

Meanwhile, Medscape is offering CME (continuing education credits required for physicians) on the topic, under the headline, “Less Medical Intervention for Home Birth Linked to Increased Neonatal Mortality Rate.” The actual text of the CME activity is more balanced in pointing out some factors we would consider positive about home birth (such as-wait for it-some of the decreased intervention rates), but it ultimately emphasizes the point that “Currently, the American College of Obstetricians and Gynecologists does not support home birth because of safety concerns and lack of scientific study.”

We, on the other hand, would emphasize the need for clearly reported, well-conducted studies, support for women’s autonomy and informed decision-making in choosing a place of birth, and systems of care that provide the best possible outcomes for women who do choose to give birth at home.

*For more information on the kind of information you should expect to see in a meta-analysis, see PRISMA statement, a set of guidelines for reporting meta-analyses and systematic reviews.

Gretchen Reynolds, writing for the Well blog at The New York Times, reports that gender still matters a great deal in health research. It’s just difficult for some scientists to remember that.

Reynolds focuses on a pair of studies by David Rowlands, MD, a senior lecturer with the Institute of Food, Nutrition and Human Health at Massey University in New Zealand, in which he attempted to determine the importance of protein in the recovery from hard exercise. The first study, completed in 2008, involved only male cyclists and found that ingesting protein had a significant long-term effect on overall athletic performance.

After Rowlands published those results, which were in line with conventional wisdom, female cyclists asked him to include them in any further studies. To his credit, he decided to repeat the entire experiment again with the female cyclists.

The results completely contradicted the original study. Not only did women fail to see benefits from ingesting protein — their legs actually felt more tired and sore.

The reason for the discrepancy — and what role estrogen plays in all this — still puzzles Rowland. In any case, the bigger lesson was obvious: excluding women from research is scientifically unsound.

The danger of using male bodies to represent all bodies became very clear once again last week when Northwestern Medicine in Chicago announced a new formula for figuring out a women’s maximum heart rate, considered a critical number in constructing an optimum workout.

The traditional formula (subtract a person’s age from 220) has led some women to experience frustration and exhaustion from workouts that should have been exhilarating, writes Tara Parker-Pope. The new formula for women, based on new research, is 206 minus 88 percent of age.

The new formula will also more accurately predict the risk of heart-related death during a stress test.

“Now we know for the first time what is normal for women, and it’s a lower peak heart rate than for men,” said Martha Gulati, MD, assistant professor of medicine and preventive medicine and a cardiologist at Northwestern Medicine and lead author of a study published June 28 in the journal Circulation. “Using the standard formula, we were more likely to tell women they had a worse prognosis than they actually did.”

“Women are not small men,” Gulati added. “There is a gender difference in exercise capacity a woman can achieve. Different physiologic responses can occur.”

Next up for Gulati: an iPhone app that will make quick calculations using the new formula.

Plus: For some historical context, the Society for Women’s Health Research provides a brief outline of efforts waged in the late 1980s and early 1990s to require that women be included in federally funded clinical research. It ended in the NIH Revitilization Act, which was signed into law in 1993.

Several prominent blogs have recently covered the story, first reported by Alice Dreger and Ellen K. Feder at  Bioethics Forum, of pediatric urologist Dix Poppas and his research involving clitoral surgery on young girls and young intersex patients to make their genitals less “masculinized” — that is, less large.

The research, conducted at New York Presbyterian Hospital, Weill Medical College of Cornell University, is troublesome for a number of reasons, including lack of indication of an underlying medical problem. In each case, the clitoris was deemed simply  too large, whatever that might have meant to the girls’ parents or the girls’ physicians.

Not only are the surgeries, as well as the accompanying attitudes and ethics, hugely problematic, but there are also issues with the follow-up study, which involved applying a cotton applicator and/or a vibrating device to determine how much nerve sensitivity was retained. Poppas was stimulating the genitalia of young children for the purposes of research, and it’s not clear to readers of the related research papers that those patients had a clear ability to consent or withdraw consent or how the potential for psychological harm was addressed.

The ethics of this research and how it was approved in the first place are quite important. But here’s another issue to consider: The articles in which this research was described were published in The Journal of Urology, a prominent journal, in October 2007 (see “Nerve Sparing Ventral Clitoroplasty: Analysis of Clitoral Sensitivity and Viability,” and “Nerve Sparing Ventral Clitoroplasty Preserves Dorsal Nerves in Congenital Adrenal Hyperplasia“).

They appeared online even earlier, in August 2007. The citations were included in the PubMed database, which is publicly accessible. So the news has been out there, for anybody to find and call attention to, for almost three years. But it didn’t cause alarm or outcry until Bioethics Forum, a project of The Hastings Center, brought the findings to the attention of a wider audience.

Another example of an awareness delay is the cervical cancer experiment in New Zealand, in which women with cervical carcinoma in situ were monitored instead of being fully treated (or informed of the lack of treatment), and many of them went on to develop invasive cervical cancer — most without ever realizing they were part of an experiment in the first place. (Here’s a slideshare presentation I did, explaining the experiment).

Initial “natural history” reports from this experiment were published in the medical literature in 1970, but there was little public attention or outcry until two women’s health activists published an investigation in 1987. In both cases, ethically problematic research was published but didn’t attract public attention or outcry for some years after the fact.

What can we do about this? Of course, many of us don’t have access to expensive journal subscriptions to read the full-text of such researchers’ questionable methodologies. We can, however, set up saved search strategies and alerts in publicly available citation databases (e.g., PubMed), and monitor the results for items that ding our warning bells.

There’s a lot of talk currently about e-patients (loosely defined as internet-savvy health consumers) with regards to researching medical conditions and treatments, but perhaps more activist-minded e-patients, and other online activists, should play a role in monitoring the broader biomedical research landscape. We know there are institutional review boards to monitor research on the front end, but what about research such as Poppas’s work, which is approved and published with little fanfare?

So, readers, what topics would you like to see in a search strategy set up to monitor these type of issues? What procedures or terms are always worth a review for the ethics and inclusion criteria? For example, I’d expect any research on prisoners should get a second look, and the combination of the clitoroplasty terms and the age groups in the Poppas citations might raise a red flag.

More broadly, how can women’s health and other human rights activists most effectively monitor the biomedical literature for ethical lapses and violations? I’m interested in hearing your ideas, and am happy to put my medical librarianship skills to work for better monitoring strategies.

An FDA advisory panel last week unanimously recommended not to approve a new drug that purports to treat hypoactive sexual desire disorder (HSDD) in women, which is defined as “low or no sexual interest to the point of distress in otherwise healthy people.”

According to Julia Johnson, the panel’s chairwoman and head of the department of obstetrics and gynecology at the University of Massachusetts Medical School, the impact of the drug flibanserin (proposed trade name: Girosa), developed by the German pharmaceutical company Boehringer Ingelheim, was “not robust enough to justify the risks.”

Indeed, this is the point many women’s health advocates have stressed all along. The flibanserin trials were considered a success by Boehringer, but the results seem less than stellar.

In a study of 1,378 premenopausal women who had been in a monogamous relationship for 10 years on average, women were randomly assigned to take 100 mg of flibanserin or a placebo daily and to record daily whether they had sex, and whether it was satisfying. Via Time magazine:

Women in the flibanserin group self-reported 2.8 sexually satisfying events in the four-week baseline period; in the final four weeks of the 24-week study period, those women reported 4.5 sexually satisfying events, a more than 50% increase. Women in the placebo group reported an increase from 2.7 events to 3.7. The difference in effect between flibanserin and the placebo — about 0.8 sexually satisfying events — was statistically significant, the drug company said, and the side effects from the drug, which included dizziness and fatigue, among others, were mild to moderate and transient.

So women taking the drug had less than one additional “sexually satisfying event” (orgasm not required) than women taking a placebo. And in the meantime, the drug caused dizziness, nausea and fatigue, particularly with long-term daily use, in some women — hardly the recipe for sexual excitement.

The FDA also considered whether the drug had increased women’s desire — a crucial element of the HSDD diagnosis, which involves low or no sexual interest to the point of distress in people who are physically healthy and not depressed — and found that the drug failed in this area.

And that’s the trickiest part. Erectile dysfunction is treated by increasing blood flow to the penis, which leads to an erection. But for women, it’s not about being physically unable to have sex — it’s that there’s little interest in sex altogether, especially troubling when one has the same long-term partner.

The construction of this as a disorder is a classic case of “disease mongering,” according to clinical psychiatrist and researcher Leonore Tiefer. The hope for a female Viagra, one pill that will “cure” women’s sexual disease, ignores the social and historical context that has a tremendous effect on female attitudes toward sex and is often part of a larger attempt to medicalize the sex lives of women.

Time magazine’s Catherine Elton interviewed Judy Norsigian, executive director of OBOS, who outlined the concern:

Attempting to treat low libido with a pill ignores the fact that many women’s level of desire is deeply affected by everyday life stress and interpersonal relationships. Add to that a cultural milieu that at once promotes shame and ignorance about women’s sexuality while wildly inflating their expectations for sex. In many cases, says Norsigian, the proper solution to a lack of sexual desire would involve a number of non-drug approaches, such as therapy, mind-body techniques and getting partners involved in the solution.

“That could be equally successful while at the same time not exposing women to the [potential] long-term adverse effects of drugs,” says Norsigian, who suggests testing drugs like flibanserin against drug-free therapies. “Moreover, the non-medication approaches often address root causes for lack of libido and thus reflect a prevention approach that is usually much wiser.”

For similar reasons, the New View Campaign has been active in opposing flibanserin, as well as previous drugs such as Intrinsa, a testosterone patch from Procter & Gamble that failed to receive FDA approval in 2004. The Campaign provides several insightful fact sheets that explain the history and side effects of flibanserin.

Particularly revealing is the fact sheet on the marketing of flibanserin [PDF], which shows how Ogilvy Public Relations, on behalf of Boehringer, has promoted HSDD as a chief cause of women’s sexual dissatisfaction — through celebrities, celebrity sexuality experts and promotional websites. Most unsettlingly, Boehringer was able to sponsor and provide editorial input for a Discovery Channel documentary — “Understanding Female Sexual Desire: The Brain Body Connection” — which has acted, in its repeated showing on TV and the web, as an infomercial for the drug.

A better film to watch would be “Orgasm Inc.: The Strange Science of Female Pleasure,” a behind-the-scenes expose of the pharmaceutical industry’s flimsy construction of female sexual dysfunction as a curable disease and the attempt to develop and market a Viagra-type solution.

A new study published in the American Heart Association’s journal Circulation looks at what American women know about the risks for cardiovascular disease and the barriers to disease prevention.

The researchers surveyed women ages 25 and older about their demographics, their knowledge about heart disease (including their awareness of heart disease as the leading cause of death for women), perceived risk factors and prevention strategies, their sources of information about heart disease, preventive actions taken in the last year and barriers to prevention. Findings were also compared to surveys on these topics conducted in 1997, 2000, 2003, and 2006 to see how the responses have changed.

Among the results, 54% of respondents correctly identified heart disease/heart attack as the leading cause of death among women. However,  a disparity exists in this knowledge. Although awareness that heart disease/heart attack is the leading cause of death has doubled in white and Hispanic women and tripled among African American women since 1997, African American, Hispanic, and Asian women are still significantly less likely to be aware of this fact than white women.

Knowledge of heart attack warning signs had not increased significantly from the 1997 findings, with 56% of women correctly listing chest pain and neck, shoulder, and arm pain, 29% correctly identifying shortness of breath, and 17%, 15%, and 7% recognizing chest tightness, nausea, and fatigue, respectively. The authors also found that only 53% of women said they would call 911 if they were having heart attack symptoms; it’s usually recommended that people experiencing heart attack symptoms call 911 right away, even if they’re uncertain of whether they are really experiencing a heart attack.

The authors also noted that many women cited beliefs about effective methods of preventing heart disease that are not currently supported by the evidence, such as use of multivitamins (69%), antioxidants (70%), and special vitamins (58%, such as vitamin A, C, or E). 19% of women still reported a belief that hormone therapy was a useful preventive method, although this has declined from the 47% who held this belief in 1997 prior to the 2002 early halt to the Women’s Health Initiative trial and the accompanying warning that postmenopausal hormone therapy could actually increase cardiovascular risk.

Women reported numerous barriers to living a heart healthy lifestyle, including family obligations/caregiving (reported by 51% of respondents), confusion in the media about what they should be doing (42%), a belief that some higher power determines their health (37%), a lack of confidence in their ability to successfully change their behavior (33%), and a lack of money or health insurance (32%), among others less frequently reported. Lack of clear communication from health care providers (19%) and language barriers (8%) were also cited as concerns.

A recent ABC news piece and two new journal articles (in The Lancet and Obstetrics and Gynecology) have drawn attention to an emergency contraception drug that is not currently available in the U.S. but apparently has been submitted to the FDA for review.

Emergency contraception pills (EC) currently available in the U.S.  are intended to be taken within 72 hours (3 days) of unprotected intercourse or contraceptive failure.  The drug new drug, ellaOne (ulipristal acetate), can be taken within 120 hours (5 days), providing a longer period in which to prevent pregnancy. [It's worth noting here that women have long been advised that existing EC options can also be taken up to 5 days after intercourse, although that's not the "official" approved recommendation on the drug inserts].

Anti-choice groups such as the American Association of Pro-Life Obstetricians and Gynecologists argue that the pill could cause abortions and be an OTC abortion pill in the U.S., using a definition of “pregnancy” that includes a non-implanted fertilized egg, a definition that is generally not medically or scientifically accepted. These arguments were also presented during debate over the approval of Plan B.

The Lancet study compared ulipristal acetate (30 mg) with levonorgestrel (1.5 mg, the drug in Plan B) among adult women in the US and UK seeking emergency contraception within 120 hours of unprotected intercourse.

The women were followed for pregnancy outcomes, and both drugs significantly reduced the expected pregnancy rate, with the outcomes demonstrating that ulipristal was not inferior to levonorgestrel at preventing pregnancy.

The researchers also looked at rates of pregnancy among those 203 women who received one of the drugs 72-120 hours after unprotected intercourse. They found reduced rates of pregnancy: 0 in the ulipristal group, and 3 pregnancies in the levonorgestrel group, a statistically greater reduction in the ulipristal group (although a couple of changes either way might make a big difference in this result).

The second study, in Obstetrics and Gynecology, also looked at efficacy of ulipristal acetate over various time periods, up to 120 hours, and seemed to demonstrate continuing efficacy beyond 72 hours.

Both studies were funded by the company that owns ulipristal acetate.

A librarian note: searching PubMed for ulipristal acetate only returns a few citations; a search for “CDB 2914″[Substance Name] OR “CDB-2914″ OR “ulipristal acetate” OR “ellaone” is more comprehensive.

A forthcoming article in the journal Contraception, “Pregnancy coercion, intimate partner violence and unintended pregnancy,” looks at whether adolescent and young women have experienced birth control sabotage, pregnancy coercion, and/or physical or sexual violence.

Researchers from UC Davis conducted a survey of 1,278 16-29 year old women seeking care in five California family planning clinics in 2008-2009. The participating women were Hispanic (30%), Black (28%), White (22%), Multiracial (7%) and “Asian/other” (13%). Pregnancy coercion was defined as being told not to use birth control by a partner, threatened with physical harm if they did not agree to get pregnant, being forced or pressured to become pregnant, having hidden birth control because of fear that the partner would become upset, or being told that the partner would have a baby with someone else or leave if they did not become pregnant.

Birth control sabotage was defined as having a partner take off a condom while having sex, put holes in a condom on purpose, take away birth control, or forced sex without a condom.

Participants were also asked about their lifetime histories of physical and sexual violence and history of unintended pregnancy.

The key findings:

• 53.4% reported having experienced partner violence
• 40.9% had experienced at least one unintended pregnancy
• 19.1% had experienced pregnancy coercion
• 15.0% had experienced birth control sabotage

The authors also reported that women who had experienced partner violence in the past were also more likely to have experienced pregnancy coercion or birth control sabotage (35% of those reporting violence compared to 15% of those not reporting violence). Women who had experienced reproductive control (coercion or sabotage) were also more likely to have experienced an unplanned pregnancy. When looking at the data by exposure to partner violence, reproductive control was associated with unintended pregnancy only among those who were exposed to partner violence.

Although the authors looked at lifetime exposures and so could not look at associations within specific relationships or the order of these events in time, one co-author of the study suggested that the associations may “explain why unintended pregnancies are far more common among abused women and teens.”

The researchers conclude that:

Comprehensive screening in clinical settings for the prevalent experiences of pregnancy coercion, birth control sabotage and partner violence should be considered a priority, particularly in the context of family planning and related programmatic efforts to reduce unintended pregnancy. Such screening may facilitate the critical work of addressing barriers to contraception among affected women and girls so as to reduce their elevated risk for unintended pregnancy.

The lead author of the study was also one of the researchers for a smaller study of intimate partner violence and birth control sabotage that we reported on in 2007.

[Note: Although I was able to get a copy of the article, it is not yet readily available online. I'll try to add a link if an abstract/full text becomes available.]

New government guidelines recommending that women start screening for breast cancer at age 50 instead of 40 set off a round of criticism this week and caused much confusion for women who for years have been told that early detection saves lives.

But a number of women’s health organizations, including Our Bodies Ourselves, the National Women’s Health Network and Breast Cancer Action, for years have warned that regular mammograms do not necessarily decrease a women’s risk of death. Premenopausal women in particular are urged to consider the risks and benefits.

In fact, the NWHN issued a position paper in 1993 recommending against screening mammography for pre-menopausal women. It was a very controversial position at the time — even more so than now. The breast cancer advocacy movement was in its infancy and efforts were focused on getting Medicare and insurance companies to cover mammograms. What the NWHN found — and other groups have since concurred — is that the potential harm from screening can outweigh the benefits for premenopausal women.

That statement is tricky, and based on the poor explanations I’ve seen that fail to specifically address the potential dangers, it’s no wonder women are frustrated. Some are even questioning whether the guidelines were unveiled as a cost-cutting measure — a sign of the “rationing” to come under health care reform. In addition to delaying routine screening until age 50, the guidelines recommend screening women between the age of 50 and 74 every two years. It’s important to keep in mind this is intended for women with no known risk factors; women in high-risk groups should start earlier, and it may be prudent to schedule more frequent mammograms.

Adding to the confusion, cancer groups are split. The American Cancer Society came out strongly against the new guidelines. The National Cancer Institute, meanwhile, said it would reconsider its own recommendations in light of new studies. Some doctors said they would proceed cautiously before revising screening advice for patients.

I don’t believe the new guidelines are politically motivated, nor are they “patronizing” to women simply because they call into question the stress related to biopsies and false positive results. Rather, the guidelines provide a useful framework for helping each of us to decide when is the best time to begin screenings and the intervals at which they should be repeated.

The guidelines are in sync with international recommendations; the World Health Organization recommends starting screening at age 50, and in Europe, mammograms are given to post-menopausal women every other year and detection rates are similar to the United States. During an interview on MSNBC on Tuesday, breast cancer expert Dr. Susan Love said the government’s guidelines bring us into line with the rest of the world and with current research. (Read more at her blog.)

You might be thinking: Wait a moment, isn’t earlier better? Why would delaying detection be in my best interest? I’m going to explain why, but let’s first take a closer look at the guidelines, which were released by the U.S. Preventative Services Task Force (USPSTF), an independent panel of experts in prevention and primary care. (The task force operates under the Agency for Healthcare Research and Quality, the research arm of the U.S. Department of Health and Human Services.)

The guidelines are an update of the 2002 USPSTF recommendation statement, which called for mammograms every one to two years, starting at age 40. Dr. Alfred Berg of the University of Washington, who chaired the task force in 2002, told The New York Times this week, “We pointed out that the benefit will be quite small.” He added that while older women experience the most benefits from the screening, mammograms still prevent only a small percentage of breast cancer deaths.

Breast cancer is the second-leading cause of cancer-related deaths in women (lung cancer is number one). According to the National Cancer Institute, about 192,370 women will be diagnosed with breast cancer in 2009, and 40,170 women will die of the disease this year. A woman who is now 40 years old has a 1.44 percent chance of being diagnosed with breast cancer over the next 10 years.

For the 2009 update, the panel, now with different members, examined the role of five screening methods in reducing breast cancer mortality rates: film mammography, clinical breast examination, breast self-examination, digital mammography, and magnetic resonance imaging. It also commissioned two studies:

1.) A targeted systematic evidence review of six selected questions relating to benefits and harms of screening.

2.) A decision analysis that used population modeling techniques to compare the expected health outcomes and resource requirements of starting and ending mammography screening at different ages and using annual versus biennial screening intervals.

Here is the summary of the task force’s findings, published in the Annals of Internal Medicine. The grades are explained here; A is the highest recommendation (meaning there’s a high certainty the benefits are substantial), and D is the lowest. A rating of I indicates evidence is insufficient or conflicting.

The USPSTF recommends against routine screening mammography in women aged 40 to 49 years. The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms. This is a C recommendation.

The USPSTF recommends biennial screening mammography for women aged 50 to 74 years. This is a B recommendation.

The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older. This is an I statement.

The USPSTF recommends against teaching breast self-examination (BSE). This is a D recommendation.

The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of clinical breast examination (CBE) beyond screening mammography in women 40 years or older. This is an I statement.

The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of either digital mammography or magnetic resonance imaging (MRI) instead of film mammography as screening modalities for breast cancer. This is an I statement.

Dr. Diana Petitti, a professor of biomedical informatics at Arizona State University and vice chair of the current task force, told The New York Times the panel knew the recommendations would surprise many women, but, she said, “We have to say what we see based on the science and the data.”

Frankly, I was surprised by the conclusion that self breast exams are not considered useful. News stories this week have included many anecdotes from women who found a lump that turned out to be cancerous, and every doctor I heard interviewed said that women should definitely contact their physician if they notice any changes in their breast. But what we’re learning is that feeling our own breasts for lumps is not statistically effective, and women who do self breast exams get twice as many biopsies.

The World Health Organization concurs: “There is no evidence on the effect of screening through breast self-examination (BSE). However, the practice of BSE has been seen to empower women, taking responsibility for their own health. Therefore, BSE is recommended for raising awareness among women at risk rather than as a screening method.”

Around 37 million mammograms are done each year. So what’s the problem there? For starters, mammograms use low-dose X-rays to examine the breast, and exposure to radiation can have a cumulative effect on the body. And they’re imperfect. About half of all premenopausal women, and one-third of postmenopausal women, have dense breasts, which makes their mammograms more difficult to read.

Mammograms produce false-positive results in about 10 percent of cases, leading to anxiety that can last for years, unnecessary and sometimes-disfiguring biopsies, and unneeded treatment, including surgery, radiation and chemotherapy — each of which present their own complications and health risks, including an increased risk of other cancers and heart disease.

According to the National Breast Cancer Coalition, U.S. estimates show a woman’s cumulative risk for a false-positive result after 10 mammograms is almost 50 percent. The risk for undergoing an unnecessary biopsy is almost 20 percent. Barbara Brenner, executive director of Breast Cancer Action, told me last year that research indicates that having more biopsies increases the risk of breast cancer, though the reason is unclear (read my post here).

Women are constantly being told “early detection saves lives,” but in reality we know some breast cancers, by the time they’re found, cannot be treated. Other cancers will never be life-threatening, and some will respond to currently available treatments. Unfortunately, the type of cancer cannot be determined at the time of diagnosis, which means we don’t know for sure whether the treatment will cause more harm than the cancer.

If you’re reading this and thinking you still want to keep that scheduled mammogram, you should certainly do so.

“No one is saying that women should not be screened in their 40s,” said Petitti, the task force vice chair. “We’re saying there needs to be a discussion between women and their doctors.”

Dr. Amy Abernethy of the Duke Comprehensive Cancer Center said she agrees with updated recommendations.

“Overall, I think it really took courage for them to do this,” she said. “It does ask us as doctors to change what we do and how we communicate with patients. That’s no small undertaking.”

Finally, I want to address the insurance question. At this point, insurance companies and Medicare administrators are saying that they will continue to pay for mammograms. Here’s what may change in the future, according to The New York Times:

The guidelines are not expected to have an immediate effect on insurance coverage but should make health plans less likely to aggressively prompt women in their 40s to have mammograms and older women to have the test annually.

Congress requires Medicare to pay for annual mammograms. Medicare can change its rules to pay for less frequent tests if federal officials direct it to. Private insurers are required by law in every state except Utah to pay for mammograms for women in their 40s.

But the new guidelines are expected to alter the grading system for health plans, which are used as a marketing tool. Grades are issued by the National Committee for Quality Assurance, a private nonprofit organization, and one measure is the percentage of patients getting mammograms every one to two years starting at age 40.

That will change, said Margaret E. O’Kane, the group’s president, who said it would start grading plans on the number of women over 50 getting mammograms every two years.

For more information, here are some good stories and links:

NPR: All Things Considered looks at the research.

Washington Post: A good overview of the guidelines and cost controversy.

ScienceBlogs: “From my perspective, these new recommendations are a classic example of what happens when the shades of gray that make up the messy, difficult world of clinical research meet public health policy, where simple messages are needed in order to motivate public acceptance of a screening test,” writes Orac. “It’s also an example where reasonable researchers and physicians can look at exactly the same evidence for and against screening at different ages and come to different conclusions based on a balancing of the potential benefit versus the cost.”

The current issue of JAMA has an article and editorial on the chronic pain experienced by some women following breast cancer surgery. This is not a topic I’ve personally read or heard much, so I was interested and surprised to read the editorial’s opening statement that “Chronic pain after breast cancer surgery occurs in approximately 50% of patients.”

The associated study paper in the journal provides more detail.  The research looked at 3,253 women in Denmark who had undergone unilateral (one-sided) breast cancer surgery in 2005-2006. The women were surveyed 2-3 years after surgery. Clinical data on the surgeries and follow-up was extracted from Danish registries, and women were surveyed about the presence or absence of pain and its location, severity, and frequency.

The authors found that 47% of the surveyed women reported pain. Of these women, 13%  reported severe pain; 39% reported moderate pain; and 48% reported light pain.

Among the 13% of women with severe pain, 77% experienced pain every day. Many of the women experiencing ongoing pain (28%) had additional contact with a physician to try to address the issue, or were taking analgesics or receiving other therapy in attempts to relieve the pain.

Younger women were more likely to report pain. There was no difference in rates of ongoing pain for mastectomy vs. breast conserving surgery, but women who had mastectomy had a higher risk of moderate to severe pain as opposed to lighter pain. Women who received adjuvant radiotherapy also had a higher risk of reporting pain. Additional women reported sensory disturbances or discomfort.

With nearly 50% of women experiencing chronic pain 2 to 3 years after surgery, it’s clear that more research on effective ways of controlling or preventing the pain needs to happen.

Chronic fatigue syndrome (CFS) is a somewhat mysterious condition, as while it causes serious impairment, the cause is currently unknown, and there is no known cure. The illness, which is characterized by a constellation of symptoms including incapacitating exhaustion, cognitive problems, nonrestorative sleep, and severe exercise intolerance (when exercise makes symptoms worse),  is thought to occur 4 times more frequently in women than in men. A new paper published by the journal Science suggests an association between chronic fatigue syndrome and a virus previously associated with prostate cancer. The virus in question is xenotropic murine leukemia virus-related virus (XMRV).

For the study, the researchers examined samples from 101 patients with chronic fatigue syndrome and 218 healthy controls to see if they could detect the virus. They were able to detect the virus in 67% of those with CFS, and 3.7% of controls, leading them to conclude that the virus is perhaps somehow associated with the disease.

The link between XMRV and either prostate cancer or chronic fatigue syndrome is not fully understood and may not be causative. The authors of the current study themselves conclude with several questions about whether the virus is a causal factor for CFS or simply more readily hosted in immunosuppressed patients. In a commentary on the findings for Science, two authors write:

There is still much that we do not understand. Whether the virus plays a causative role in either chronic fatigue syndrome or prostate cancer is unknown. For example, XMRV infection might, coincidentally, be more frequent in the same geographical region as a cluster of patients with chronic fatigue syndrome. And individuals with either disease might be more readily infected due to immune activation.

The research team plans further investigation into the association, including whether – because both are a type of virus called a retrovirus – drugs for the treatment of HIV may have some effect against CFS.

Scientific American and Not Exactly Rocket Science (at ScienceBlogs) have additional summary with discussion in the comments. For more information on Chronic Fatigue Syndrome, see the webpage of the CFIDS Association of America.

A new study in The Lancet looks at hormone replacement therapy, and concludes that while the combination of estrogen and progestin doesn’t increase women’s risk of lung cancer, it increases their risk of dying from the disease. This finding has generated a fair bit of media coverage, but – although the issue of HRT and lung cancer is an important one – the study itself is perhaps not as definitive as that coverage might suggest.

The authors analyzed data from the Women’s Health Initiative study, a trial of estrogen plus progestin hormone therapy in postmenopausal women that was stopped early when the associated health risks (including cardiovascular disease and breast cancer) were found to exceed the benefits. For this analysis, they looked at data on the incidence and mortality rates of all lung cancer, small-cell lung cancer, and non-small-cell lung cancer.

They found:

78 women in the combined hormone therapy group who had received a diagnosis of lung cancer died during follow-up, compared with 49 in the placebo group (0·12% vs 0·08%; HR 1·50, 1·05—2·14, p=0·03). Of these deaths, 73 (94%) in the combined hormone therapy group and 40 (82%) in the placebo group were directly attributed to lung cancer by chart review (HR 1·71, 1·16—2·52, p=0·01).

The impact of the study is limited, as the authors acknowledge, because of the unplanned post-hoc analysis (a statistically weak method), and because of the small number of lung cancers in the population (fewer thank 130 out of more than 16,000 women studied) and the absence of information on treatment after diagnosis. An accompanying commentary in the journal explains that “data on the effect of oestrogens on both the incidence of lung cancer and outcomes from lung cancer are controversial,” with conflicting findings and limited study designs.

Due to its limitations, the new Lancet paper does not provide strong evidence on whether hormone replacement therapy significantly raises the risk of death from lung cancer, but it may encourage future research and suggest something that should, as the authors conclude, “be considered before the initiation or continuation of combined hormone therapy in postmenopausal women, especially those with a high risk of lung cancer, such as current smokers or long-term past smokers.”

Related: The National Cancer Institute provides information on hormone replacement therapy and risks for breast, ovarian, colorectal, and endometrial cancer and related issues here.

When you, or more likely your doctor, reads an article in a medical journal on the efficacy of a certain drug, it would be nice to know whether the article includes research or writing contributions from people or companies other than the credited author — such as, say, the pharmaceutical company that makes the drug.

But according to a new study by the editors of the Journal of the American Medical Association, some of the top medical journals have published a significant number of articles written by ghostwriters without notifying readers about any potential conflict of interest.

“In the scientific literature, ghostwriting usually refers to medical writers, often sponsored by a drug or medical device company, who make major research or writing contributions to articles published under the names of academic authors,” write Duff Wilson and Natasha Singer in The New York Times, which covered the study last week.

The Times has published several other articles on this topic recently, including news that Wyeth pharmaceutical company paid ghostwriters to produce 26 scientific papers promoting the benefits and downplaying the risks of hormone replacement therapy. (Read our coverage, including Stephen Colbert’s take.)

Considering what’s at stake — treatment decisions and patient care — it’s remarkable that articles in well-respected, peer-reviewed journals are not fully transparent.

The JAMA editors created an anonymous, online questionnaire for authors of journal articles. The authors were asked to self-report their own behavior. Authors of 630 articles responded; of them, 7.8 percent acknowledged other people worked on the articles and the contributions were substantial enough that they should have been listed as authors.

The New England Journal of Medicine had the highest rate of ghostwriting at 10.9 percent. The rate was 7.9 percent in JAMA; 7.6 percent in The Lancet; 7.6 percent in PLoS Medicine; 4.9 percent in The Annals of Internal Medicine; and 2 percent in Nature Medicine.

“It was very compelling, and I find it quite shocking, to be honest,” Ginny Barbour, chief editor of PLoS Medicine, the journal of the Public Library of Science, said after the findings were unveiled at an international meeting of journal editors in Vancouver. “We are a journal that has very tough policies, very explicit policies on ghostwriting and contributorship, and I feel that we’ve basically been lied to by authors.”

Read more from PLoS here.

The news comes just weeks after the National Institutes of Health (NIH), a federal agency that invests more than $30 billion in medical research each year, most of which is awarded through competitive grants to researchers at universities, medical schools and other research institutions, came under fire for not promoting a clear policy on ghostwriting with regards to NIH-funded researchers and institutions.

In a letter to the NIH, which was obtained by The New York Times, Sen. Charles Grassley (R-Iowa) identified researchers at Columbia University and University of Maryland who were recipients of NIH grants and who have signed on to ghostwritten publications. Academic institutions traditionally have also taken a hands-off approach.

Two recent studies of home birth have generated a lot of attention online.

The first (.pdf), published in the British Journal of Obstetrics and Gynaecology, examines fetal and newborn outcomes of planned home and planned hospital births among low-risk women.

For this retrospective study, the authors identified all low-risk women (more than 500,000 of them) who gave birth in the years 2000-2006 in Netherlands and who were in midwife-led care at the onset of labor. They explain that in the Netherlands, independent primary care midwives care for low-risk pregnant women, but women are transferred to “secondary” care with an obstetrician if any risks arise during pregnancy, or to a hospital if problems occur during a planned home birth.

Approximately 30% of women in the Netherlands give birth at home. The authors compared women by intended place of birth (home, 60.7%; hospital, 30.8%; or unknown, 8.5%) for intrapartum fetal death, intrapartum and neonatal death up to 24 hours, and intrapartum and neonatal death up to 7 days and admission after birth to a neonatal intensive care unit (NICU).

Women were included as low risk if they gave birth at 37-42 weeks gestation to a single fetus, with no known medical or obstetric risk factors, cephalic (head down) presentation, no previous c-section, no previous postpartum hemorrhage, no prolonged (>24 hours) rupture of membrane, no congenital abnormality, and no intrauterine death prior to onset of labor. Women not meeting these criteria were not considered low risk and so were not included. Included women who planned a home birth may have been transferred to a hospital for reasons such as failure to progress, an abnormal fetal heart rate pattern, or meconium staining.

The authors explain that after controlling for confounding factors (maternal and gestational age, parity, ethnic background, and socioeconomic status), there was no significant difference between groups on measures of perinatal mortality, and no significant difference between planned home vs. planned hospital groups on risk of NICU admission.

The authors note that the study has some limitations, including its retrospective design and missing NICU data for 50% of the non-teaching hospitals. It’s strengths are its very large size, available national registry data, and comparison of groups of women who were considered low risk until the onset of labor, rather than comparing low-risk women planning home births to mixed hospital birth populations that include known high risk patients (i.e., those who were never candidates for home birth).

An editorial on the paper notes that the approach to maternity care in the Netherlands is rather different from that in some other locations, explaining that “maternity services in the Netherlands are set up to meet the demand for home births, transport is good, and distances short,” but also calls the large study “reassuring about the relative safety of planning home births if women are low risk.

Jennifer Block (“Pushed”) wrote about this study and home birth in general last month for Babble, and the UK’s National Health Service offers this summary.

A recent retrospective cohort study, published in the Canadian Medical Association Journal, was conducted in British Columbia, Canada, and compared 2,889 planned home births attended by registered midwives to planned hospital births attended by registered midwives (4,752) or physicians (5,331). Women planning to give birth at home had to be medically eligible for home birth at the onset of labor. These eligibility criteria excluded women with certain pre-existing conditions (such as heart disease), pregnancy-related diseases such as gestational diabetes requiring insulin and hypertension, multiple fetuses, non-cephalic presentation, premature or post-dates pregnancies (<36 or >42 weeks), >1 previous c-section, and other factors. The planned hospital births included in the study also met the home birth eligibility criteria.

The authors’ primary outcome of interest was the rate of perinatal death, defined as stillbirth after 20 weeks’ gestation or death in the first 7 days of life, although stillbirths occurring before the onset of labor or in women who gave birth before 37 weeks were excluded from all groups.

The outcomes were analyzed by planned place of birth. Specific information on reasons for transfer does not seem to be available, but 78.8% of those women who planned a home birth with a midwife had one, and 96.9% of those who planned to be attended by a midwife in a hospital did so.

The authors found no statistically significant differences in the low risk of perinatal mortality between the 3 groups, at 0.35/1,000 for planned home birth, 0.57/1,000 for planned hospital birth with a midwife, and 0.64/1,000 for planned hospital birth with a physician. There were no deaths from 8-28 days of life. The authors also observed lower rates of obstetric interventions for planned home births with midwives than with either hospital group – the full text with tables of these secondary outcomes is freely available online.

The authors note the ability to compare place of birth without confounding from the type of provider (assuming physicians are more likely to conduct interventions than midwives), a strength of the Dutch study as well. But the authors also explain that “our findings do not extend to settings where midwives do not have extensive academic and clinical training.” They also note the possibility that some unknown difference between groups that influenced choice of birth place may have affected the outcomes, but that “our data indicate that screening for eligibility by registered midwives can safely support a policy of choice of birth setting.”

Amy Romano at Science & Sensibility and Lauredhel at Hoyden About Town have both written about the study, with a fair bit of discussion at both places.

Citations: de Jonge A, van der Goes BY, Ravelli AC, Amelink-Verburg MP, Mol BW, Nijhuis JG, Bennebroek Gravenhorst J, Buitendijk SE. Perinatal mortality and morbidity in a nationwide cohort of 529,688 low-risk planned home and hospital births. BJOG. 2009 Aug;116(9):1177-84.
Janssen PA, Saxell L, Page LA, Klein MC, Liston RM, Lee SK. Outcomes of planned home birth with registered midwife versus planned hospital birth with midwife or physician. CMAJ. 2009 Aug 31. [Epub ahead of print]

AHRQ has posted a new evidence report, Treatment for Overactive Bladder in Women. For these reports, a team of folks reviews and evaluates the quality of the existing evidence on a topic, and looks at how that evidence addresses some key questions – in this case on prevalence and incidence of overactive bladder, treatment outcomes, comparisons of treatments, modifiers of outcomes, and costs.

I am particularly enthused about this one not only because it’s related to women’s health, but because it was done by the Evidence-based Practice Center (EPC) at my larger workplace, and I was actually involved in this topic through input on the search strategy and reviewing abstracts and full-text papers for inclusion/exclusion in the analysis. My colleague Rebecca Jerome was more deeply involved in the process, including some of the write-up, and is listed as one of the investigators.

Here’s the link to the PDF, if you’re interested. OBOS has some related content on urinary urgency and frequency and interstitial cystitis here, which touches on the confusion about treatment/mistreatment of urinary problems in women. Similarly, the AHRQ report notes that while overactive bladder is somewhat common and effectively resolving it may be important for women’s quality of life, the effects of the available treatments (including drug treatment) are considered “modest,” with little high quality literature available on the topic to guide treatment choices. As the Executive Summary concludes: “Women and their care providers deserve better information to guide their choices.”

[Cross-posted from Women's Health News]

Most users of hormonal birth control have heard warnings that the drugs may increase risk of blood clots. Two new studies in the journal BMJ examine this risk, and attempt to characterize the amount of risk by how long women were on the drugs and the type of hormone. In general, they find the highest risk when women first start taking the pill, decreased risk with decreased dose, and a lower risk with levonorgestrel than with other progestagens.

The first, a case-control study conducted in the Netherlands, compared 1,524 pre-menopausal women who had experienced a deep vein thrombosis or pulmonary embolism with 712 women who had not (the control group). All of the participants completed a questionnaire on risk factors for venous thrombosis such as family history, pregnancy, and oral contraceptive use, and were further interviewed about their oral contraceptive use.

The researchers report a fivefold increase in risk for venous thrombosis associated with oral contraceptive use. The also found different levels of risk by the type of contraceptive in use – compared to women who did not use the drug, those using a contraceptive containing levonorgestrel (the most frequently used in the study) had an almost fourfold increase in risk (odds ratio 3.6). Risk also appeared to increase 5.6-fold for those containing gestodene, 6.3-fold for drospirenone, 6.8-fold for cyproterone acetate, and 7.3-fold for desogestrel. Risk seemed to increase with higher dosages, and to decrease over time – women had the greatest risk as new users in the first 3 months (odds ratio 12.6) which declined to the average 5-fold increased risk after one year.

The second is a cohort study using registry data to track Danish women over time for various types of thromboses and oral contraceptive use. The paper uses “woman years” as a measure of the participants and explains that the study covered 10.4 million woman years of observation (2 years of observation of 5 people, for example, would be 10 person-years). They report that “The overall absolute risk of venous thrombosis per 10,000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29.”

These authors also found decreased risk over time, with the highest risk in the first year, a decreased risk with decreased estrogen dose, and a higher risk with contraceptives containing desogestrel, gestodene, or drospirenone were associated with a higher risk of venous thromboembolism than those containing levonorgestrel.

The BMJ issue also includes an editorial on the studies – which notes that while the absolute risk of blood clots is low, providers may need to consider these findings in selecting contraceptives with individual patients – and links to a recent review of different contraception options for women.