Is the bar high enough for screening breast ultrasounds for breast cancer?

The stormy landscape of the breast, as seen
on ultrasound. At top center (dark circle) is
a small cyst. Source: Wikimedia Commons.
Credit: Nevit Dilmen.
By Laura Newman, contributor

In a unanimous decision, FDA has approved the first breast ultrasound imaging system for dense breast tissue “for use in combination with a standard mammography in women with dense breast tissue who have a negative mammogram and no symptoms of breast cancer.” Patients should not interpret FDA’s approval of the somo-v Automated Breast Ultrasound System as an endorsement of the device as necessarily beneficial for this indication and this will be a thorny concept for many patients to appreciate.

If the approval did not take place in the setting of intense pressure to both inform women that they have dense breasts and lobbying to roll out all sorts of imaging studies quickly, no matter how well they have been studied, it would not be worth posting.

Dense breasts are worrisome to women, especially young women (in their 40s particularly) because they have proved a risk factor for developing breast cancer. Doing ultrasound on every woman with dense breasts, though, who has no symptoms, and a normal mammogram potentially encompasses as many as 40% of women undergoing screening mammography who also have dense breasts, according to the FDA’s press release. Dense breast tissue is most common in young women, specifically women in their forties, and breast density declines with age.

The limitations of mammography in seeing through dense breast tissue have been well known for decades and the search has been on for better imaging studies. Government appointed panels have reviewed the issue and mammography for women in their forties has been controversial. What’s new is the “Are You Dense?” patient movement and legislation to inform women that they have dense breasts.

Merits and pitfalls of device approval
The approval of breast ultrasound hinges on a study of 200 women with dense breast evaluated retrospectively at 13 sites across the United States with mammography and ultrasound. The study showed a statistically significant increase in breast cancer detection when ultrasound was used with mammography.

Approval of a device of this nature (noninvasive, already approved in general, but not for this indication) does not require the company to demonstrate that use of the device reduces morbidity or mortality, or that health benefits outweigh risks.

Eitan Amir, MD, PhD, medical oncologist at Princess Margaret Hospital, Toronto, Canada, said: “It’s really not a policy decision. All this is, is notice that if you want to buy the technology, you can.”

That’s clearly an important point, but not one that patients in the US understand. Patients hear “FDA approval” and assume that means a technology most certainly is for them and a necessary add-on. This disconnect in the FDA medical device approval process and in what patients think it means warrants an overhaul or at the minimum, a clarification for the public.

Materials for FDA submission are available on the FDA website, including the study filed with FDA and a PowerPoint presentation, but lots of luck, finding them quickly. “In the submission by Sunnyvale CA uSystems to FDA, the company stated that screening reduces lymph node positive breast cancer,” noted Amir. “There are few data to support this comment.”

Is cancer detection a sufficient goal?
In the FDA study, more cancers were identified with ultrasound. However, one has to question whether breast cancer detection alone is meaningful in driving use of a technology. In the past year, prostate cancer detection through PSA screening has been attacked because several studies and epidemiologists have found that screening is a poor predictor of who will die from prostate cancer or be bothered by it during their lifetime. We seem to be picking up findings that don’t lead to much to worry about, according to some researchers. Could new imaging studies for breast cancer suffer the same limitation? It is possible.

Another question is whether or not the detected cancers on ultrasound in the FDA study would have been identified shortly thereafter on a routine mammogram. It’s a question that is unclear from the FDA submission, according to Amir.

One of the problems that arises from excess screening is overdiagnosis, overtreatment, and high-cost, unaffordable care. An outcomes analysis of 9,232 women in the US Breast Cancer Surveillance Consortium led by Gretchen L. Gierach, PhD, MPH, at the National Institutes of Health MD, and published online in the August 21 Journal of the National Cancer Institute, revealed: “High mammographic breast density was not associated with risk of death from breast cancer or death from any cause after accounting for other patient and tumor characteristics.” –Gierach et al., 2012

Proposed breast cancer screening tests
Meanwhile, numerous imaging modalities have been proposed as an adjunct to mammography and as potential replacements for mammography. In 2002, proponents of positron emission tomography (PET) asked Medicare to approve pet scans for imaging dense breast tissue, especially in Asian women. The Medicare Coverage Advisory Commission heard testimony, but in the end, Medicare did not approve it for the dense-breast indication.

PET scans are far less popular today, while magnetic resonance imaging (AKA MR, MRI) and imaging have emerged as as adjuncts to mammography for women with certain risk factors. Like ultrasound, the outcomes data is not in the bag for screening with it.

In an interview with Monica Morrow, MD, Chief of Breast Surgery at Memorial Sloan-Kettering Cancer Center, New York, several months ago concerning the rise in legislation to inform women about dense breasts, which frequently leads to additional imaging studies, she said: “There is no good data that women with dense breasts benefit from additional MR screening.” She is not the only investigator to question potentially deleterious use of MR ahead of data collection and analysis. Many breast researchers have expressed fear that women will opt for double mastectomies, based on MR, that in the end, may have been absolutely unnecessary.

“There is one clear indication for MR screening,” stressed Morrow, explaining that women with BRCA mutations should be screened with MRI. “Outside of that group, there was no evidence that screening women with MR was beneficial.”

At just about every breast cancer meeting in the past two years, the benefits and harms of MR and other proposed screening modalities come up, and there is no consensus in the field.  It  should be noted, though, that plenty of breast physicians are skeptical about broad use of MR– not just generalists outside of the field. In other words, it is not breast and radiology specialists versus the US Preventive Services Task Force – a very important message for patients to understand.

One thing is clear: as these new technologies gain FDA approval, it will be a windfall for industry. If industry is successful and doctors are biased to promoting these tests, many may offer them on the estimated 40% of women with dense breasts who undergo routine mammograms, as well as other women evaluated as having a high lifetime risk.  The tests will be offered in a setting of unclear value and uncertain harms. Even though FDA has not approved breast MRI for screening dense breasts, breast MR is being used off label and it is far more costly than mammography.

When patients raise concerns about the unaffordability of medical care, they should be counseled about the uncertain benefit and potential harms of such a test. That may be a tall bill for most Americans to consider: it’s clear that the more is better philosophy is alive and well. Early detection of something, anything, even something dormant, going nowhere, is preferable to skipping a test, and risking who-knows-what, and that is something, most of us cannot imagine at the outset.

[Today's post is from Patient POVthe blog of Laura Newman, a science writer who has worked in health care for most of her adult life, first as a health policy analyst, and as a medical journalist for the last two decades. She was a proud member of the women’s health movement. She has a longstanding interest in what matters to patients and thinks that patients should play a major role in planning and operational discussions about healthcare. Laura’s news stories have appeared in Scientific American blogs, WebMD Medical News, Medscape, Drug Topics, Applied Neurology, Neurology Today, the Journal of the National Cancer Institute, The Lancet, and BMJ, and numerous other outlets. You can find her on Twitter @lauranewmanny.]

Ed note: The original version of this post contains a posted correction that is incorporated into the version you’ve read here.

The opinions in this article do not necessarily conflict with or reflect those of the DXS editorial team. 

Diversity in Science Carnival #14: Women’s History Month–Exploring the role of women in the STEM enterprise

Women in Science, via the Smithsonian.

“We must believe that we are gifted for something.” Marie Curie

Image of a real Rosie the Riveter from the
Women’s History Month site.
It’s tempting to cast the role of women in STEM (Science, Technology, Engineering, and Math) as one of struggles and battles because of their sex, rather than as one of contributions because of their minds. But for Women’s History Month and this Diversity in Science Carnival #14, our focus is the role of women in the enterprise of STEM. There’s more to a woman than her sex and her struggles in science–there is, after all, the enormous body of work women have contributed to science.

 

Our history is ongoing, but we can start with a look back. Thanks to the efforts of the Smithsonian Institution Archives, we can put faces to the names of some of the female STEMmers of history. In a presentation of photographs in an 8 by 9 space, we can see the images of 72 women who contributed to the enterprise of STEM, many of them involved with the Smithsonian in some capacity. As their clothes and the dates on the photos tell us, these women were doing their work in a time when most women didn’t even wear pants.  
Some are Big Names–you’ve probably heard of Marie Curie. But others are like many of us, women working in the trenches of science, contributing to the enterprise of STEM in ways big and small. Women like Arlene Frances Fung, whose bio tells us she was born in Trinidad, went to medical school in Ireland, and by 1968 was engaged in chromosome research at a cancer institute in Philadelphia. From Trinidad to cancer research, her story is one of the millions we could tell about women’s historical contributions to science, if only we could find them all. But here there are 72, and we encourage you to click on each image, look at their direct gazes, ponder how their interest in science and knowledge trumped the heavy pressures of social mores, and discover the contributions these 72 women made, each on her own “little two inches wide of ivory.”

For more on historical and current women in science, you can also see Double X Science’s “Notable Women in Science” series, curated by Adrienne Roehrich.

And then there are the women STEMmers of today, who likely are, according to blogger Emma Leedham writing at her blog Pipettes and Paintbrushes, still underpaid. Leedham also mulls here what constitutes a role model for women–does it require being both a woman and a scientist, or one or the other?

Laurel L. James
Laurel L. James, writing at the University of Washington blog for the school’s SACNAS student chapter, answers with her post, “To identify my role as a woman in science: I must first honor my mother, my family and my past.” Her mother was the first “Miss Indian America,” and Laurel is a self-described non-traditional student at the school, where she is a graduate student in forest resources. She traces her journey to science, one that involved role models who were not scientists but who, as she writes, showed her “how to hang onto the things that are important with the expectation of getting something in return all the while, persevering and knowing who you are; while walking with grace and dignity.” I’d hazard that these words describe many a woman who has moved against the currents of her society to contribute something to the sciences.

A great site, Steminist.com, which features the “voices of women in science, tech, engineering, and math,” runs a series of interviews with modern-day STEMmers, including Double X Science’s own Jeanne Garbarino, and Naadiya Moosajee, an engineer and cofounder of South African Women in Engineering. You can follow Naadiya on Twitter here. Steminist is also running their version of March Madness, except that in honor of Women’s History Month, we can choose “Which historical women in STEM rock (our) world.” The 64 historical STEMinists in the tourney are listed here and include Emily Warren Robling (left), who took over completion of the Brooklyn Bridge when her husband’s health prevented his doing so; she is known as the first woman field engineer. Double X Science also has a series about today’s women in science, Double Xpression, which you can find here.

Today, you can find a woman–or many women–in STEM just about anywhere you look, whether it is as a government scientist at NOAA like Melanie Harrison, PhD, or at NASA. It hasn’t always been that way, and it can still be better. But women have always been a presence in STEM. In the 18thand 19th centuries, astronomer Caroline Herschellabored away through the dark hours of just about every night of her adult life, tracking the night sky. Today, women continue these labors, and STEM wouldn’t be what it is today without women like Herschel willing to stay up all night with the skies or spend days on end in the field or lean over a microscope for hours just to add a tiny bit more to what we know about our world and our universe.

                            

Caroline Herschel
For women in science, we’re there–at night, in the lab, in the field–because we love science. But as the non-science role models seem to tell us, we stick to it–and can stick with it–because we had role models in and out of science who showed us that regardless of our goals, our attitudes and willingness to move forward in spite of obstacles are really what drive us to success in STEM careers. Among the links I received for this carnival was one to Science Club for Girls, which is sponsoring a “Letter to My Young Self” roundup for Women’s History Month. The letters I’ve read invariably have that “stick with it” message, but one stood out for me, and I close with a quote from it.

It’s a letter by Chitra Thakur-Mahadik, who earned her PhD in biochemistry and hemoglobinopathy from the University of Mumbai and served as staff scientist a Mumbai children’s hospital for 25 years. She wrote to her younger, “partially sighted” self that, “The future is ahead and it is not bad!” She goes on to say, “Be fearless but be compassionate to yourself and others… be brave, keep your eyes and ears open and face the world happily. What if there are limitations? Work through them with awareness. –Yours, Chitra”
Links and resources for women in STEM, courtesy of D.N. Lee

Stay tuned for the April Diversity in Science Carnival #15: Confronting the Imposter Syndrome. This topic promises to resonate for many groups in science. I’m pretty sure we’ve all felt at least of twinge of imposter syndrome at some point in our education and careers.  Your editor for this carnival will be the inimitable Scicurious, who  blogs at Scientific American and Scientopia.




UPDATE: Carnival #15 is now available! Go read about imposter syndrome, why it happens, who has it, and what you can do about it. 

By Emily Willingham, DXS managing editor 

How helpful are dense-breast right-to-know laws?

A doctor reviews a digital mammogram, pointing to a possible cancer.
Credit: National Cancer Institute.
By Laura Newman, DXS contributor
In a victory for the dense-breast patient movement, Governor Jerry Brown (D-CA) signed legislation last week requiring that doctors who discover that women have dense breasts on mammography must inform women that:

§  dense breasts are a risk factor for breast cancer;
§  mammography sees cancer less well in dense breasts than in normal breasts; and
§  women may benefit from additional breast cancer screening.

The California law goes into effect on April 1, 2013. It follows four states (Connecticut, Texas, Virginia, and New York) with similar statutes. All have enjoyed solid bipartisan support. Rarely do naysayers or skeptics speak up.
Young women who are leading the charge often bring lawmakers the story of a young constituent, diagnosed with a very aggressive, lethal cancer that was not shown on film-screen mammography. The Are You Dense? patient advocacy group engages patients on Facebook, where women share their experiences with breast cancer, organize events, and lobby for legislation. Individual radiologists work with the advocacy groups, but many radiology groups and breast surgeons do not endorse these laws.


A Closer Look at Breast Cancer Data

Living in an age when information is viewed as an entitlement, knowledge, and power, many physicians find it hard to argue against a patient’s right to know. Can sharing information be a mistake? Some epidemiologists think so. Otis W. Brawley, MD, FACP, Chief Medical & Scientific Officer, American Cancer Society, says: “I really worry when we legislate things that no one understands. People can get harmed.” Numerous issues have to be worked out, according to Brawley. For one, he explains: “There is no standard way to define density.” Additionally, “even though studies suggest that density increases the risk of cancer, these cancers tend to be the less serious kind, but even that is open to question,” Brawley says. “We in medicine do not know what to do for women who have increased density.”

A study of more than 9,000 women in the Journal of the National Cancer Institute revealed that women with very dense breasts were no more likely to die than similar patients whose breasts were not as dense. “When tumors are found later in more dense breasts, they are no more aggressive or difficult to treat,” says Karla Kerlikowske, MD, study coauthor, and professor of medicine and epidemiologist at the University of California San Francisco. In fact, an increased risk of death was only found in women with the least dense breasts.


The trouble is what is known about dense breasts is murky. Asked whether he backs advising women that dense breasts are a risk factor for breast cancer, Anthony B. Miller, MD, Co-Chair of the Cancer Risk Management Initiative and a member of the Action Council, Canadian Partnership Against Cancer, and lead investigator of the Canadian National Breast Cancer Screening Study, says: “I would be very cautious. The trouble is people want certainty and chances are whatever we find, all we can do is explain.”

Women in their forties, who are most likely to have dense breasts (density declines with age) may want to seek out digital mammography. In studies comparing digital mammography to film-screen mammography in the same women, digital mammography has been shown to improve breast cancer detection in women with dense breasts. Findings from the Digital Mammographic Imaging Screening Study, showed better breast cancer detection with digital mammography. But digital mammography is not available in many areas.  Moreover, Miller explains: “We do not know if this will benefit women at all.  It is very probable that removal of the additional small lesions will simply increase anxiety and health costs, including the overdiagnosis of breast cancer, and have no impact upon mortality from breast cancer.”


Additional imaging studies sound attractive to people convinced that there is something clinically significant to find. But as I pointed out in my last post, many radiologists and breast physicians contend that there is no evidence that magnetic resonance imaging or any other imaging study aids breast cancer screening in women with dense breasts. Brawley notes: “These laws will certainly lead to more referral for MRI and ultrasound without clear evidence that women will benefit (lives will be saved.) It’s clear that radiologists will make more money offering more tests.” Miller adds: “A number of doctors are trying to capitalize on this and some of them should know a lot better.”


Many Advocates Question More Tests, Statutes

Even though the “Are You Dense?” campaign has been instrumental in getting legislation on the books across the county, other advocacy groups and patient advocates want research, enhanced patient literacy about risks and benefits of procedures. Many recall mistakes made that led women down the path of aggressive procedures. In that group is the radical Halsted mastectomy, used widely before systematic study, but once studied,  found no better than breast-conserving surgery for many cancers, and bone marrow transplants, also found to be ineffective, wearing, and costly.

Jody Schoger, a breast cancer social media activist at @jodymswho engages women weekly on twitter at #bcsm, had this to say on my blog about the onslaught of additional screening tests:

“What is needed is not another expensive modality… but concentrated focus for a biomarker to indicate the women who WILL benefit from additional screening. Because what’s happening now is an avalanche of screening, and its subsequent emotional and financial costs, that is often far out of proportion to both the relative and absolute risk for invasive cancer. I simply don’t think more “external” technology is the answer but one that evolves from the biology of cancer.”

Eve Harris @harriseve, a proponent of patient navigation and patient literacy, challenged Peter Ubel, MD, professor of business administration and medicine, at Duke University, on his view of the value of patient empowerment on the breast density issue. In a post on Forbes, replicated in Psychology Today, Ubel argued that in cases where the pros and cons of a patient’s alternatives are well known, for example, considering mastectomy or lumpectomy, patient empowerment play an important role. “But we are mistaken to turn to patient empowerment to solve dilemmas about how best to screen for cancer in women with dense breasts,” he writes.


Harris disagrees, making a compelling case for patient engagement:

“I think that we can agree that legislative interference with medical practice is not warranted when it cannot provide true consumer protection. But the context is the biggest culprit in this situation. American women’s fear of breast cancer is out of proportion with its incidence and its mortality rate. Truly empowering people—patients would mean improving health literacy and understanding of risk…”


But evidence and literacy take time, don’t make for snappy reading or headlines, and don’t shore up political points. Can we stop the train towards right-to-inform laws and make real headway in women’s health? Can we reallocate healthcare dollars towards effective treatments that serve patients and engage them in their care? You have to wonder.
[Today's post is from Patient POVthe blog of Laura Newman, a science writer who has worked in health care for most of her adult life, first as a health policy analyst, and as a medical journalist for the last two decades. She was a proud member of the women’s health movement. She has a longstanding interest in what matters to patients and thinks that patients should play a major role in planning and operational discussions about healthcare. Laura’s news stories have appeared in Scientific American blogs, WebMD Medical News, Medscape, Drug Topics, Applied Neurology, Neurology Today, the Journal of the National Cancer Institute, The Lancet, and BMJ, and numerous other outlets. You can find her on Twitter @lauranewmanny.]

The opinions in this article do not necessarily conflict with or reflect those of the DXS editorial team. 

Is there glamour in science? There are certainly no scientists in Glamour

Hedy Lamarr: actress, pinup “girl,” and, oh, yeah,  inventor.

Is there glamour in science?

The answer to that question depends on what you mean by “glamour.” Do we get to dress up in clicky heels and walk red carpets? Well, we can do the heels, sure, but red carpets aren’t a frequent feature in the life of most scientists, unless you count that horrible red patterned stuff conference hotels seem to like so much.

Do we travel the world? Sure–see “conference” in previous paragraph. Our conferences can take us to places we never might have gone were it not for our abiding interest in stars or fruit flies or the finer points of protein signaling. If you’re the kind of scientist who does field work with hyenas or needs samples from Antarctica, then your travel can be even more exotic. Do we, like actresses or singers or Kim Kardashian, get to spend our days doing what we love, bringing IT to the world? Hell, yes, we do.

Heels (optional), travel to far-flung locations, passion for what we do, bringing IT. Yep…there’s some glamour in science. And you know what? I’d hazard that while we’re doing it, we’re feeling “beyond empowered.”

The reason I ask is that Glamour magazine just release its “Women of the Year” awards. Before I talk about recipients–or non-recipients–I would like to review the magazine’s mission statement:

Glamour is a magazine that translates style and trends for the real lives of women. Our award-winning editorial covers the most pressing interests of our 12.4 million readers: from beauty, fashion and health to politics, Hollywood and relationships. We’re often optimistic, always inclusive, beyond empowering and can always separate the Dos from the Don’ts. Our readers live for fashion, live for beauty and most of all, live for Glamour.

You’ll see that they seek to cover the “most pressing interests” of their readers, that they are “always inclusive” and “beyond empowering,” and that their readers live for, among other things, beauty and Glamour. I am going to pretend that wedged in there, tacit but present, between “health” and “politics” is “science.” Why? Because nothing but science can bring you solid information about your health. Because politics have a powerful influence over how that science can be used for your health. And because if you live for beauty, science can bring you beauty that takes your breath away, like this:

A stellar nursery in our intergalactic neighborhood.

And this:
Scanning electron microsope image of the lower surface of a leaf from a black walnut tree.

Scientists are the explorers, the discovers, and the investigators…and sometimes, their work becomes art.

Given that science can be so glamorous, so beautiful, so empowering, you might think that the editors of Glamour, which offers its readers all three, might have included a scientist in its “Women of the Year” awards.

They did not. 

That is not to diminish the fabulous, empowered women they did include. Gloria Steinem? Check. Gabrielle Giffords? Oh, yes. The beautiful, gutsy, empowered Esraa Abdel Fattah? Yes, and thank you. Arianna Huffington’s there…although I find what her HuffPo Website countenances for health–including women’s health–sometimes less than empowering. There’s an artist, there’s a fashion designer, there’s…um…Laura Bush and her daughters and…J. Lo. Lea Michelle, a grown woman and another Woman of the Year, is depicted chirpily exclaiming that “I would be happy to be a high school student forever.”

It’s a mixed bag. But in that bag, search as you will, you will find no scientists. Women who live glamorous lives, traveling, engaging, empowered and empowering. Women like Mireya Mayor, who despite her walking the walk in Pink Boots and a Machete, despite identifying a new species of lemur (video), despite her high-profile as an explorer and on television, does not fit the bill for Glamour.


One reason you find no scientists is that Glamour doesn’t seem to have a “Woman of the Year” category that includes science. They’ve selected some women who truly are inspirations, some that make you think, “Whuh?” (Kim Kardashian as “Entrepreneur of the Year” for UK Glamour comes to mind), and even some girls. Kardashians not withstanding, when Amy Poehler makes a list like this, you’ve got to give the editors some credit. 

So, I ask. Can the editors at Glamour give women in science some credit, too? Women like Elodie Ghedin, 2011 Macarthur Fellow and virologist whose work directly addresses critical public health issues? Or Ada Yonath, who was awarded the 2009 Nobel Prize in Chemistry for working on that tiniest of cellular structures, the ribosome? Or Elizabeth Blackburn or Carol W. Greider, who received the Nobel Prize in Physiology or Medicine in 2009 for their work in unlocking some of the secrets to aging? Or Susan Niebur, former NASA astrophysicist and four-time breast cancer survivor who has worked tirelessly while fighting inflammatory breast cancer to promote breast cancer research, awareness of inflammatory breast cancer (the cancer that kills without a lump), science outreach, and women in science?

Glamour editors…women need science and girls and women need inspiration from scientists. Your list of “Women of the Year” includes women who are enormously inspirational and who have done immeasurable good for women. For 2012, please consider that women scientists fit that definition, too, and can also bring the glamour of passion and empowerment to your readers. Those 12.4 million women will thank you.

By Emily Willingham

Hormonal birth control explainer: a matter of health

Politics often interferes where it has no natural business, and one of those places is the discussion among a teenager, her parents, and her doctor or between a woman and her doctor about the best choices for health. The hottest button politics is pushing right now takes the form of a tiny hormone-containing pill known popularly as the birth control pill or, simply, The Pill. This hormonal medication, when taken correctly (same time every day, every day), does indeed prevent pregnancy. But like just about any other medication, this one has multiple uses, the majority of them unrelated to pregnancy prevention.

But let’s start with pregnancy prevention first and get it out of the way. When I used to ask my students how these hormone pills work, they almost invariably answered, “By making your body think it is pregnant.” That’s not correct. We take advantage of our understanding of how our bodies regulate hormones not to mimic pregnancy, exactly, but instead to flatten out what we usually talk about as a hormone cycle. 

The Menstrual Cycle

In a hormonally cycling girl or woman, the brain talks to the ovaries and the ovaries send messages to the uterus and back to the brain. All this chat takes place via chemicals called hormones. In human females, the ovarian hormones are progesterone and estradiol, a type of estrogen, and the brain hormones are luteinizing hormoneand follicle-stimulating hormone. The levels of these four hormones drive what we think of as the menstrual cycle, which exists to prepare an egg for fertilization and to make the uterine lining ready to receive a fertilized egg, should it arrive. 

Fig. 1. Female reproductive anatomy. Credit: Jeanne Garbarino.
In the theoretical 28-day cycle, fertilization (fusion of sperm and egg), if it occurs, will happen about 14 days in, timed with ovulation, or release of the egg from the ovary into the Fallopian tube or oviduct (see video–watch for the tiny egg–and Figure 1). The fertilized egg will immediately start dividing, and a ball of cells (called a blastocyst) that ultimately develops is expected to arrive at the uterus a few days later.
If the ball of cells shows up and implants in the uterine wall, the ovary continues producing progesterone to keep that fluffy, welcoming uterine lining in place. If nothing shows up, the ovaries drop output of estradiol and progesterone so that the uterus releases its lining of cells (which girls and women recognize as their “period”), and the cycle starts all over again.


A typical cycle

The typical cycle (which almost no girl or woman seems to have) begins on day 1 when a girl or woman starts her “period.” This bleeding is the shedding of the uterine lining, a letting go of tissue because the ovaries have bottomed out production of the hormones that keep the tissue intact. During this time, the brain and ovaries are in communication. In the first two weeks of the cycle, called the “follicular phase” (see Figure 2), an ovary has the job of promoting an egg to mature. The egg is protected inside a follicle that spends about 14 days reaching maturity. During this time, the ovary produces estrogen at increasing levels, which causes thickening of the uterine lining, until the estradiol hits a peak about midway through the cycle. This spike sends a hormone signal to the brain, which responds with a hormone spike of its own.

Fig. 2. Top: Day of cycle and phases. Second row: Body temperature (at waking) through cycle.
Third row: Hormones and their levels. Fourth row: What the ovaries are doing.
Fifth row: What the uterus is doing. Via Wikimedia Commons
In the figure, you can see this spike as the red line indicating luteinizing hormone. A smaller spike of follicle-stimulating hormone (blue line), also from the brain, occurs simultaneously. These two hormones along with the estradiol peak result in the follicle expelling the egg from the ovary into the Fallopian tube, or oviduct (Figure 3, step 4). That’s ovulation.
Fun fact: Right when the estrogen spikes, a woman’s body temperature will typically drop a bit (see “Basal body temperature” in the figure), so many women have used temperature monitoring to know that ovulation is happening. Some women also may experience a phenomenon called mittelschmerz, a pain sensation on the side where ovulation is occurring; ovaries trade off follicle duties with each cycle.  

The window of time for a sperm to meet the egg is usually very short, about a day. Meanwhile, as the purple line in the “hormone level” section of Figure 2 shows, the ovary in question immediately begins pumping out progesterone, which maintains that proliferated uterine lining should a ball of dividing cells show up.
Fig. 3. Follicle cycle in the ovary. Steps 1-3, follicular phase, during
which the follicle matures with the egg inside. Step 4: Ovulation, followed by
the luteal phase. Step 5: Corpus luteum (yellow body) releases progesterone.
Step 6: corpus luteum degrades if no implantation in uterus occurs.
Via Wikimedia Commons.
The structure in the ovary responsible for this phase, the luteal phase, is the corpus luteum (“yellow body”; see Figure 3, step 5), which puts out progesterone for a couple of weeks after ovulation to keep the uterine lining in place. If nothing implants, the corpus luteum degenerates (Figure 3, step 6). If implantation takes place, this structure will (should) instead continue producing progesterone through the early weeks of pregnancy to ensure that the lining doesn’t shed.

How do hormones in a pill stop all of this?

The hormones from the brain–luteinizing hormone and follicle-stimulating hormone– spike because the brain gets signals from the ovarian hormones. When a girl or woman takes the pills, which contain synthetics of ovarian hormones, the hormone dose doesn’t peak that way. Instead, the pills expose the girl or woman to a flat daily dose of hormones (synthetic estradiol and synthetic progesterone) or hormone (synthetic progesterone only). Without these peaks (and valleys), the brain doesn’t release the hormones that trigger follicle maturation or ovulation. Without follicle maturation and ovulation, no egg will be present for fertilization.

Assorted hormonal pills. Via Wikimedia Commons.
Most prescriptions of hormone pills are for packets of 28 pills. Typically, seven of these pills–sometimes fewer–are “dummy pills.” During the time a woman takes these dummy pills, her body shows the signs of withdrawal from the hormones, usually as a fairly light bleeding for those days, known as “withdrawal bleeding.” With the lowest-dose pills, the uterine lining may proliferate very little, so that this bleeding can be quite light compared to what a woman might experience under natural hormone influences.

How important are hormonal interventions for birth control?

Every woman has a story to tell, and the stories about the importance of hormonal birth control are legion. My personal story is this: I have three children. With our last son, I had two transient ischemic attacks at the end of the pregnancy, tiny strokes resulting from high blood pressure in the pregnancy. I had to undergo an immediate induction. This was the second time I’d had this condition, called pre-eclampsia, having also had this with our first son. My OB-GYN told me under no uncertain terms that I could not–should not–get pregnant again, as a pregnancy could be life threatening.

But I’m married, happily. As my sister puts it, my husband and I “like each other.” We had to have a failsafe method of ensuring that I wouldn’t become pregnant and endanger my life. For several years, hormonal medication made that possible. After I began having cluster headaches and high blood pressure on this medication in my forties, my OB-GYN and I talked about options, and we ultimately turned to surgery to prevent pregnancy.

But surgery is almost always not reversible. For a younger woman, it’s not the temporary option that hormonal pills provide. Hormonal interventions also are available in other forms, including as a vaginal ring, intrauterine device (some are hormonal), and implants, all reversible.

                                            

One of the most important things a society can do for its own health is to ensure that women in that society have as much control as possible over their reproduction. Thanks to hormonal interventions, although I’ve been capable of childbearing for 30 years, I’ve had only three children in that time. The ability to control my childbearing has meant I’ve been able to focus on being the best woman, mother, friend, and partner I can be, not only for myself and my family, but as a contributor to society, as well.

What are other uses of hormonal interventions?

Heavy, painful, or irregular periods. Did you read that part about how flat hormone inputs can mean less build up of the uterine lining and thus less bleeding and a shorter period? Many girls and women who lack hormonal interventions experience bleeding so heavy that they become anemic. This kind of bleeding can take a girl or woman out of commission for days at a time, in addition to threatening her health. Pain and irregular bleeding also are disabling and negatively affect quality of life on a frequent basis. Taking a single pill each day can make it all better. 


Unfortunately, the current political climate can take this situation–especially for teenage girls–and cast it as a personal moral failing with implications that a girl who takes hormonal medications is a “slut,” rather than the real fact that this hormonal intervention is literally maintaining the regularity of her health.

For some context, imagine that a whenever a boy or man produced sperm, it was painful or caused extensive blood loss that resulted in anemia. Would there be any issues raised with providing a medication that successfully addressed this problem?

Polycystic ovarian syndrome. This syndrome is, at its core, an imbalance of the ovarian hormones that is associated with all kinds of problems, from acne to infertility to overweight to uterine cancer. Guess what balances those hormones back out? Yes. Hormonal medication, otherwise known as The Pill.  

Again, for some context, imagine that this syndrome affected testes instead of ovaries, and caused boys and men to become infertile, experience extreme pain in the testes, gain weight, be at risk for diabetes, and lose their hair. Would there be an issue with providing appropriate hormonal medication to address this problem?

Acne. I had a friend in high school who was on hormonal medication, not because she was sexually active (she was not) but because she struggled for years with acne. This is an FDA-approved use of this medication.

Are there health benefits of hormonal interventions?

In a word, yes. They can protect against certain cancers, including ovarian and endometrial, or uterine, cancer. Women die from these cancers, and this protection is not negligible. They may also help protect against osteoporosis, or bone loss. In cases like mine, they protect against a potentially life-threatening pregnancy.

Speaking of pregnancy, access to contraception is “the only reliable way” to reduce unwanted pregnancies and abortion rates [PDF]. Pregnancy itself is far more threatening to a girl’s (in particular) or woman’s health than hormonal contraception.

Are there health risks with hormonal interventions?

Yes. No medical intervention is without risk. In the case of hormonal interventions, lifestyle habits such as smoking can enhance risk for high blood pressure and blood clots. Age can be a factor, although–as I can attest–women no longer have to stop taking hormonal interventions after age 35 as long as they are nonsmokers and blood pressure is normal. These interventions have been associated with a decrease in some cancers, as I’ve noted, but also with an increase in others, such as liver cancer, over the long term. The effect on breast cancer risk is mixed and may have to do with how long taking the medication delays childbearing. ETA: PLoS Medicine just published a paper (open access) addressing the effects of hormonal interventions on cancer risk.
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By Emily Willingham, DXS Managing Editor
Opinions expressed in this piece are my own and do not necessarily reflect the opinions of all DXS editors or contributors.

HIV+ doesn’t mean you can’t have children

Prenatal care and treatment access are big factors.

By Laura Newman     

Last week, the media got all excited about the possibility of a cure for HIV perinatal transmission. What was lacking was the recognition that the public remains largely ignorant about HIV in pregnant women. Yet with good wellness care, prevention, HIV testing, and medication,HIV  transmission from mother to child can be close to zero. The public needs to know that women who are pregnant and HIV positive can also live good-quality lives, as can their children.

CDCgraphicHIVThanks to Dr. Judy Levison, an obstetrician/gynecologist whose career centers on caring for HIV-pregnant women, I began to learn how scientific advancements in HIV-care make it possible for pregnant women with HIV and HIV-positive men to have children and not transmit the virus to their newborns. In the midst of this learning experience, I found out that a young woman I know, “Angela*,” was HIV positive and wanted to plan a pregnancy. I was shocked; I knew plenty of gay men with HIV, but rarely had I met a woman who had contracted the virus. Planning a pregnancy while being infected with HIV was something that I couldn’t imagine.

“Angela” is married and has lived with HIV for some years, with a low viral load by taking good care of herself and taking recommended antiretroviral therapy, when needed. She sought artificial insemination, one of several options available to HIV-affected couples. It worked. When she was planning her pregnancy, her parents were resistant. They worried that even though she is healthy now, that might change. They couldn’t imagine being saddled with taking care of a young child. Her parents’ resistance reminded me of the old coming-out stories we used to hear and how parents adapted to learning their child is gay. To their credit, both parents soon rose to the occasion. Angela and her spouse have a healthy toddler, and the grandparents love spending time with him.

Angela’s story isn’t everyone’s story. The hubbub at the recent 20th Conference on Retroviruses and Opportunistic Infections was not on the “functional cure” of the baby born to a pregnant woman with HIV, but on why, in this day and age, the mother doesn’t seem to have received the recommended prenatal care and antiretroviral therapy herself. Under what circumstances did she deliver? How did mom and baby get lost in the healthcare system? It’s far too easy to be captivated by a potential breakthrough and forget that plenty of people don’t get access to basic science-backed care that prevents HIV transmission in the first place.

As I describe below and as Angela’s experience illustrates, a lot of evidence shows that it is very safe for women with HIV to get pregnant, have healthy babies, and not transmit HIV to their children. Unfortunately, for many pregnant women with HIV, harsh judgments and inaccurate assumptions often carry the day. Let’s just say that HIV-positive moms and their kids have not earned the acceptance allotted to, say, a Magic Johnson, who has had HIV for decades, and with good HIV and wellness care, lives a good-quality life.

These inroads in science-based HIV prevention and care that have helped Johnson so much lag behind in poor and minority communities in the United States and low-resource countries around the world. HIV disproportionally affects African-Americans in the United States, and access to care, Medicaid cuts, and poverty reduce the chance that many people in need will receive good state-of-the-art prevention (regular testing, practicing safe sex, not sharing drug needles) and wellness care. Perinatal transmission could well rise in these communities.

Facing down ignorance

At first, being pregnant was not easy for Angela — not because her pregnancy was hard (it was not) — but because of the uneasiness some of her coworkers expressed about her becoming pregnant as an HIV-positive woman. Even though Angela worked in healthcare, some of her coworkers thought she had no business being pregnant. When she complained to her supervisor, the manager urged Angela to take it upon herself to educate staff about scientifically proven treatments for pregnant women with HIV that help moms stay well and prevent transmission to the baby. Angela asked instead for an in-service training, which was scheduled. Her colleagues’ attitudes turned around after the in-service.

It meant a lot to her to change the culture.

Angela had a normal term delivery, gave birth to a healthy baby, who is now a toddler, with no sign of HIV infection. Angela’s viral load remains undetectable. They are living healthy, high-quality lives like many other families, moms, and children.

The parents and prenatal planning

The ideal in the setting of HIV infection is that both partners are involved in preconception planning. Prevention of transmission of HIV from an HIV-positive father to an HIV-negative mom and fetus is now possible. The door is now open to HIV-positive men and women who want families but have HIV. Any plans they had to become parents have not simply vanished.

HIV research has advanced to the point that we now know that if HIV-positive individuals work with knowledgeable medical providers and have good access to proven practices, parents and children do quite well. Essential practices include:

  • Before trying to conceive, people should take antiretroviral drugs and have their infection under control, shown by a low viral load or undetectable levels of the virus (“undetectable” levels vary, depending on the lab) in their blood;
  • Couples are instructed to have unprotected sex only when the woman is ovulating. Current guidelines recommend using an ovulation prediction kit, which you can purchase at most drugstores.
  • Artificial insemination is another option that HIV-affected couples are using, as Angela did.
  • HIV testing is recommended routinely for all pregnant women, as well as for all non-pregnant adults and teens.
  • If a woman learns during her pregnancy for the first time that she is HIV infected, she can work with her healthcare provider to stay healthy, prevent mother-to-child transmission, and prevent passing HIV to her partner.

 

In general, people infected with HIV who are not pregnant begin taking anti-HIV medications when their CD4 counts fall below 500 cells/mm3 (HIV targets these immune cells and destroys them, compromising a person’s immunity). The medication regimen during pregnancy depends on whether or not you are taking medication to improve your own health or just your baby’s. In many cases, healthy women delay starting antiretroviral medication until the second trimester, which is when all women should be on HIV medication. However, HIV medication and interactions with other drugs and the fetus are complicated and require consultation with a physician. If women are diagnosed later in a pregnancy, they should start HIV drugs then. You can find detailed recommendations here.

During childbirth, women whose viral loads are still undetectable can have normal vaginal deliveries. However, according to the National Institutes of Health and other authorities, scheduled cesarean delivery at 38 weeks of gestation is recommended to reduce perinatal transmission of HIV for women with HIV-RNA levels >1,000 copies/mL or unknown HIV levels near the time of delivery, regardless of whether they were taking recommended antiretroviral drugs during pregnancy. The guidelines state that when there is a low rate of transmission (viral loads lower than 1000 copies/mL), the benefits of a scheduled c-section are unclear. Dr. Levison, an obstetrician/gynecologist at Baylor College of Medicine, Houston, TX, says that in her practice, women rarely need a cesarean section.

The newborn child

In the United States, breastfeeding is discouraged because HIV can be transmitted in breast milk. According to the Centers for Disease Control and Prevention (CDC), the risk for HIV transmission goes up as much as 45%. However, the topic of breastfeeding remains controversial. In healthy women with no HIV history, the broad consensus is that breastfeeding is best, giving babies excellent nutrition and helping the infant bond with mom. And many parts of the world have problems with sanitation and dirty water, making breastfeeding preferable to mixing formula. Outside of the US, according to Levison, in the UK, breastfeeding guidelines are more liberal. Furthermore, in some cultures, women are afraid not to breastfeed for fear that they will be outed as having an HIV infection, according to Levison, so many treating physicians adapt practice to the culture, preferences of the mom. Internationally, for example, in Africa, women often breastfeed and remain on antiretroviral drugs during that time. Formula is also costly. In the US, poor moms are eligible for formula through the federal Women’s Infants and Children’s nutritional support program.

Besides breastfeeding, HIV-positive moms need to know that pre-chewing of food before feeding baby is a transmission risk.

As soon as a woman goes into labor and during childbirth, the infantmust begin a six-week course of the antiretroviral medication zidovudine (AZT). Current guidelines also state that the baby should be tested for HIV at 14 to 21 days, at 1 to 2 months, and again at 4 to 6 months. If the viral load remains undetectable after two tests, the baby is considered to not have gotten HIV.

Resolving resource disparities

The moms, dads, and kids with HIV have enormous potential to live healthy lives for decades on proven antiretroviral drugs.

In fact, a December 2012 CDC Fact Sheet states that the number of women with HIV giving birth in the United States increased approximately 30% from 6,000 to 7,000 in 2000 to 8700 in 2006. During that same time frame, the estimated number of perinatal infections per year in all 50 states and 5 dependent areas continued to decline.

It’s not all good news, though, because of marked disparities in resource allocation and pre- and perinatal care. According to CDC data, 63% of perinatal infections were in blacks/African-Americans; 22% were in Hispanics/Latinos, and 13% were in whites. That leaves a lot of work to be done in enhancing targeted prevention programs.

Another recent milestone is that the US Preventive Services Task Force is finally about to endorse universal HIV testing, long after the CDC backed such a move in 2006. This milestone is important to because it is also linked to health reform.  All public and private health plans are required to provide coverage for U.S. Preventive Services Task Force-recommended preventive services without patient copayments.

With this availability, perhaps women might learn about an HIV infection before they become pregnant, giving them time to have their own treatment in place before it is too late to protect the baby. The case report of the baby cured of HIV gives a lot of hope, but even more preferable would be preventing HIV infection in the first place, through safe sex and not exchanging needles. Once people become infected, for whatever reason, their lives should no longer be viewed as if they are at in a holding pattern until death.

The world needs to know that just like every other mom, dads and pregnant women with HIV can parent children, stay healthy, and not transmit the virus to their babies. Paramount in this is universal HIV testing for adults and teens, prevention programs, and ensuring scientifically proven treatment of the mother before, during, and after her pregnancy.

*Named changed to protect identity. Continue reading