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Monthly Archives: February 2011

ResearchBlogging Editor’s Selections: PMDD

Just a quick note to let you all know that my PMDD post was chosen by both Krystal D’Kosta and Jason Goldman for their Editor’s Selections this week over at ResearchBlogging.org.

Join me in a conversation about hormonal contraceptives! Eat free food!

Women in the United States use hormonal contraceptives more than any other nation in the world. Doctors and patients in other countries report a hesitance to prescribe hormonal contraceptives for off-label use (to improve the skin, or regulate the cycle) where most pharmaceutical advertisements in the US celebrate exactly those uses.

Why do women in the US use hormonal contraceptives more frequently? How did you and your doctor decide that this prescription was right for you?

If you live in or near Champaign-Urbana, we would like to have you come participate in a focus group on exactly this topic! We would like to validate a survey that will be used online, but also get freeform responses from real women about their real experiences.

Please email us to participate! We can answer any questions you may have. You must be:

  • Over eighteen years old
  • Female
  • Have been prescribed hormonal contraceptives at least once

Participation involves:

  • Filling out an eligibility survey and indicating your time preference for the focus group (5 minutes)
  • Attending a focus group, where you will fill out a survey and discuss your broader experiences with hormonal contraceptives (90 minutes)

We will provide you with some tasty snacks during the focus group. So far we have found that participants have really loved being a part of this, because it’s given them a chance to reflect on their own contraceptive choices. Join us! Email us today! You will be helping us put together a comprehensive research program to understand why US women take hormonal contraceptives far more than women from other developed countries.

IRB approval for this message: #12269, amendment 02/22/2010

Tag-teaming research blogging: Me and Sci do it up, PMDD-style

When I was in college, my favorite hangout was the basement of the Harvard Book Store, where they had the used books and cheap remainders (they were also across the street from my freshman dorm, Wigglesworth, and yes, that is a most excellent name). I worked my way through several sci-fi and fantasy series, and got nearly all my Women’s Studies books, because of that one lovely room.

One night in my freshman year I was browsing the philosophy section with a new boyfriend, a person with whom I often felt inferior and less-educated. I saw an author name on the spine of an old hardcover and, hoping to impress the boyfriend, pointed it out. “Hobbes Machiavelli, I’ve read stuff by him,” I said. I arched my eyebrows with what I hoped was an air of intelligence.

The boyfriend, and a nearby witness, both turned towards me. “Hobbes and Machiavelli are two different people,” he said slowly.

As a blush crept up my face, I realized several things: the excerpt of “The Prince” I had barely skimmed in high school was by Niccolo Machiavelli, Hobbes was a totally different dude, and my boyfriend thought I was a posturing idiot.

It’s a good idea to know what you’re talking about before opening your mouth.

* * *
ResearchBlogging.orgThese days, if I don’t know the answer to something, I don’t try to fake it. Recently, a Twitter follower suggested I write on this New Scientist story and the empirical article upon which it was reporting on brain activity, hormones and Premenstrual Dysphoric Disorder. As I am not an expert on issues of the brain, rather than try to be I enlisted brilliant neuroscientist Scicurious to do tag-team blog posts where we could each cover the material where we had expertise. I had a few thoughts about the way the New Scientist article author framed the study, and about the hormone analyses. So I’ll talk about that, and Sci will cover BRAINZ in this post.

What is this study about?

Rapkin et al (2011) seek to understand why a minority of women experience Premenstrual Dysphoric Disorder (PMDD), a suite of premenstrual behaviors that include severe and debilitating irritability, depression and anxiety. They used PET scans to look at brain stuff (cue Scicurious) and also looked at hormone concentrations to see if the reproductive hormones that decline in the premenstrual phase had anything to do with it. They found no difference in hormone concentrations between control and PMDD women, but did find variation in cerebellar activity by menstrual phase. You need to read Scicurious’s take on this, because she provides important background and context to the study of the cerebellum for mood.

The New Scientist piece makes a lot of the potential effect of progesterone on GABA receptors in the brain, but as far as I can tell the article itself does not measure GABA receptors. Progesterone, allopregnanolone and GABA are all interrelated and important chemicals when it comes to mood (Concas et al 1998), but like I said, since the study didn’t actually look at GABA, I’m not going there. Sci has also made some important points about this issue, and on what the study authors found (which is admittedly cool) with what they discuss around GABA (which might be a wee bit of a stretch).

Nits to pick with New Scientist

Zukerman, the author of the New Scientist piece, begins her piece, entitled “Why women get anxious at ‘that time of the month’” with this:

“Is it that time of the month? These are the words no man should ever utter. How about this for a diplomatic alternative: “Are your GABA receptors playing up?”

You may be spot on. It seems that these brain cells are to blame for some women’s monthly mood swings.

Many women feel a little irritable before menstruating, but up to 8 per cent suffer extreme symptoms, including anxiety, depression and fatigue.”

There are a few things that trouble me about this. First, without citing any actual incidence of this symptom, the author claims that many women suffer from irritability before their period. This just perpetuates the idea that irritability is a common premenstrual trait, when the premenstrual phase is an incredibly variable period. This is despite the fact that at most only eight percent of women actually get these symptoms to the point that they are debilitating (the two studies the study authors cite give a 5% and 8% incidence, so 8% may be high).

From a public health or science research perspective, eight percent of reproductively aged women is a pretty significant quantity. I absolutely want more research to be done on PMDD and, full disclosure, I’m running some pilot studies to work on it in the future myself. However, these results don’t necessarily translate to women who may just get a little irritable or experience other mild behavioral symptoms before their period.

And that is why both the title and the “Is it that time of the month” joke at the start of the story were misleading. Besides its obvious sexism, where any female behavior that deviates from the pleasing and passive risks eliciting that question, the link here in the mind of a popular reader is that women’s behavior is governed by hormone and brain interactions more generally than the paper actually implies.

So, to reiterate: PMDD impacts maybe eight percent of reproductively aged women (notice that I keep specifically referencing “reproductively-aged women,” which further shrinks the pool of women down to those between menarche and menopause). This is nothing to sneeze at. But this isn’t everyone.

Hormones

In order to see if there were differences in hormone concentrations between normal and PMDD women, Rapkin et al (2011) took blood on the days of the PET scans: this translated into one follicular phase (first half of the cycle, between menses and ovulation) and one late luteal phase collection (the week or so before the next menses). They found no difference in the mean concentrations of estradiol and progesterone between the two groups, at either time period.

Table 1 from Rapkin et al (2011). None of these differences between groups are significant according to the authors, but they didn’t report p-values anywhere I could find.

There are several problems with this. First, the sample size is tiny. I have certainly been known to run analyses with fewer subjects, but the way I and other folks who do hormone work get around this is to sample each individual many more times. When collecting hormone information on reproductively-aged women, for instance, you want to collect a minimum of one menstrual cycle’s worth of data… every single day.

More power!

My advisor raised me right, and so I did a power analysis of the data the study authors provided. A power analysis is a way to determine the statistical power of a test. You can do it beforehand to determine an appropriate sample size for your experiment, or afterwards if you didn’t find something statistically significant and don’t know if your analysis was effective. When there are small but important differences between two groups, but the sample size is also small, your statistical test can be insignificant and thus miss that important difference.

Let’s take the hormone and time period that should be the most meaningful: progesterone in the late luteal phase. PMDD women had 5.50 ± 5.27 ng/mL, and control women had 6.76 ± 7.53 ng/mL. If we say that the smallest difference between these two groups that would be interesting is around 6 ng/mL (just splitting the difference between the two standard deviations, but this is pretty generous), then according to my calculations this test only has a power of about 60%. Therefore, 40% of the time a test with a sample size this small wouldn’t catch a potentially important difference between the groups. To put it into more perspective, the standard is to have a power of at least 80%.

What’s blood got to do with it?

On Fertile Ground: A Natural History of Human Reproduction
On Fertile Ground, by Peter T. Ellison. Go to the Amazon page to embiggen the image and you’ll see the plastic tube one of the women is holding to collect spit.


Most people with a clinical background or doing a more clinical collaboration seem to be needle-happy. That is, when they want to measure hormones, they take it out of your arm rather than from the many other places you can get it: blood spots (using a little lancet on your finger), saliva, urine, and feces. This will some day be a blog post in its own right.

Here is the short answer: saliva is very often better than venous blood. Hormones are secreted from their organs in a pulsatile way, meaning they are released in short bursts, which leads to measurements going up and down quickly. Since they circulate in the blood, serum measurements of hormones are likely to pick up this noise. This is yet another reason why only two samples for each of the twenty four subjects is troubling. There are other reasons, related to what version of the hormone you are measuring when getting it from blood, spit or elsewhere, the higher compliance and greater frequency of sampling you can do with saliva, and the fact that you don’t have to stick your subjects or increase their risk of infection.

The only studies looking at variation in hormones across the cycle in menstrually-related mood disorders use blood (Bloch et al 1998, Rubinow et al 1988). The Bloch et al 1998 measures 10 women with PMS and 10 controls using serum every day for a cycle (hooray, every day!) but they measure testosterone, cortisol, and other hormones not comparable to this study. Plus, they are looking at women with PMS, not PMDD, which is a much more broadly-defined syndrome. It would be harder to find a difference between these two groups than controls and women with PMDD.

The Rubinow et al 1988 is old enough that I can’t get it online, the abstract says nothing about how frequently the hormones are measured or the number of women in the study, and I don’t know how strictly they define menstrual disorders (again, as opposed to the rather strictly-defined PMDD).

Variation is the spice of life

My last issue with the hormones is with the two windows during which they measured them. Women were measured in their follicular phase anywhere from 8-12 days into their cycle for the first measurement; then the late luteal phase measurement was 10-14 days after a measured LH surge (which occurs around midcycle).

Here is the kind of variation I see when I measure women’s hormone concentrations every day. What you’re looking at is salivary estradiol (pmol/L) measured daily in over twenty Polish women, aligned by midcycle drop date. The first graph is all the women together, the second is the average and standard deviation.

Individual Polish women’s estradiol concentrations.

Average Polish women’s estradiol concentrations.

Here is salivary progesterone from the same population, aligned by the end of the cycle. Again, the first graph is everyone individually, the second is average and standard deviation.

Individual Polish women’s progesterone concentrations.

Average Polish women’s progesterone concentrations.

A few important things to note: this isn’t the same way the study authors aligned their data (though the way I have shown it here is more physiologically meaningful) and the units are different. However, if you look at about the times when the study authors were taking their measurements – mid to late follicular phase and late luteal phase – you see a TON of variation between those days, both within and between women. This is why a single measurement in that general window is, in essence, of no use. You have way too much noise in a single measurement to be able to begin to say anything about differences between groups.

The punchline

PMDD is very likely related to hormone concentrations – if not in their average values between groups, then in how those hormones differentially impact brain functioning (the brain sensitivity stuff Sci discusses so well). But we won’t know these potential differences if we don’t gather the hormone data correctly. Just because brain scans are cool — and really, they are and I applaud the study authors for doing stuff that I simply cannot do and finding interesting results — doesn’t mean you can give the hormones the short shrift.

References

Bloch M, Schmidt PJ, Su TP, Tobin MB, & Rubinow DR (1998). Pituitary-adrenal hormones and testosterone across the menstrual cycle in women with premenstrual syndrome and controls. Biological psychiatry, 43 (12), 897-903 PMID: 9627744

Concas A, Mostallino MC, Porcu P, Follesa P, Barbaccia ML, Trabucchi M, Purdy RH, Grisenti P, & Biggio G (1998). Role of brain allopregnanolone in the plasticity of gamma-aminobutyric acid type A receptor in rat brain during pregnancy and after delivery. Proceedings of the National Academy of Sciences of the United States of America, 95 (22), 13284-9 PMID: 9789080

Rapkin AJ, Berman SM, Mandelkern MA, Silverman DH, Morgan M, & London ED (2011). Neuroimaging evidence of cerebellar involvement in premenstrual dysphoric disorder. Biological psychiatry, 69 (4), 374-80 PMID: 21092938

Rubinow DR, Hoban MC, Grover GN, Galloway DS, Roy-Byrne P, Andersen R, & Merriam GR (1988). Changes in plasma hormones across the menstrual cycle in patients with menstrually related mood disorder and in control subjects. American journal of obstetrics and gynecology, 158 (1), 5-11 PMID: 2962499

Support scientists, support the sciences, support US innovation

Innovation and creativity are strong, valued traits in the US. Scientific and technological progress are marked by these two traits, long hours, hard work and collaboration. I got into biological anthropology because I believed I could make a real difference with my work and that it would translate into improving the lives of women in the US and around the world. I wanted to look at the modern problems of our ancient bodies, like PCOS and endometriosis, explore their origins and understand how to prevent them.

There are two issues at stake here in the conversation about the proposed House cuts via HR 1. The first is the survival of young investigators like me, the second the vibrancy of public universities like the one where I work.

I am in my third year as a tenure-track professor in a field that straddles the social and life sciences – my work is expensive by anthropological standards, but probably cheap by other basic science standards. I am on an NIH R21 proposal (no score yet) as a far-down-the-list collaborator. I am in my third submission at the NSF as a PI. Were I to do my work at the level I want, I would need over $100,000 a year in direct funding, ideally much more. So far I have received two small internal grants that, together, don’t cover a year of work. I have found some very interesting ways to do some cheap yet awesome science, but it takes a lot longer to do it this way than to do it with money. I don’t have any publications in the pipeline from this work yet (thankfully this will change any day now), in part because of its difficulty and in part because I spend all my waking hours writing grants and teaching.

Public universities used to get their money from, you know, the public. But funding has been reduced at the state and federal level, to the point that public universities survive on two sources of income: overhead from the grants faculty produce, and tuition from students. Thus, public universities recruit out-of-state students and increase their overall tuition, and we faculty frantically try to fit in one more grant proposal in time for the next grant cycle.

If young investigators are starved, if public universities are starved, we lose some of the greatest resources this country has to offer both in the production of innovative science and the education of the majority of our citizens.

Please read the note below and call your Congresscritters tomorrow.

Dear Colleague,

For months the new House leadership has been promising to cut billions in federal funding in fiscal year (FY) 2011. Later this week the House will try to make the rhetoric a reality by voting on HR 1, a “continuing resolution” (CR) that would cut NIH funding by $1.6 billion (5.2%) BELOW the current level – reducing the budget for medical research to $29.4 billion!
We must rally everyone – researchers, trainees, lab personnel – in the scientific community to protest these draconian cuts. Please go to [this link] for instructions on how to call your Representative’s Washington, DC office today! Urge him/her to oppose the cuts to NIH and vote against HR 1. Once you’ve made the call, let us know how it went by sending a short email to the address provided in the call instructions and forward the alert link to your colleagues. We must explain to our Representatives how cuts to NIH will have a devastating impact on their constituents!

Sincerely,

William T. Talman, MD
FASEB President

hat tip Isis, drdrA, ProfinTraining, and many others

Agora: for women in science

Agora is the women in science community developed by the L’Oreal Foundation. Recently I was asked to write a piece for them that talks about my work. You can find it here.

A snippet to entice you:

“The reason it’s so important to me that I be that activist scientist – someone whose work is informed by an understanding of the biases inherent in the process of science, and who promotes a deeper understanding of science to the general public – is that women’s health is something that many non-experts opine about, providing sometimes dangerous disinformation.”

Who are you and what are you doing here? The results

National Women's Day

Thanks to Ed Yong and a number of other very smart people, I was inspired after Science Online 2011 to perform a survey of my readers to figure out who comes here, why they do, and what they’d like to see more of. I enjoy engaging with other science writers, bloggers, and fellow anthropologists, really I do. But I hoped to gain some insight into how I might reach an even broader audience, to increase awareness of the kinds of science I do and that I find interesting. There are political ramifications to having a lay population completely unaware of the basic functioning of the female body, particularly around reproduction, when we have so many strong feelings about it. Feelings will always win in a one-sided fight: put it up against evidence, though, and at least some people will start to operate more rationally.

Science Online 2011 taught me a few other things in terms of how to reach that audience. By bringing in a personal element, showing enthusiasm, or giving the reader more things to look at than a wall of text, I could invite different kinds of people in. As everyone now knows, you can try DMing Ed Yong (hee hee, sorry Ed!). I tried to do those things in subsequent posts. And so, this happened:

Figure 1. My hits from the first day of #scio11 to yesterday. Eep.

My survey went from the 17th of January until the 21st or so; I stopped at sixty respondents. As you might imagine, my readership has changed.

That said, I think I learned a lot from the survey, so I want to share it with you and see if we can broaden the conversation.

Who are you?

The people who filled out my survey were about my age, were my ethnicity (European), and were mostly women (I suspect the f:m ratio would have been even higher if I hadn’t taunted Twitter at one point that the female respondents were beating the males). Here are the graphs (notice that the bars/pie slices represent absolute numbers of respondents, and percentages are listed next to each choice):

I regret the way I wrote the ethnicity question. I was trying to figure out how to ask people’s ethnicity from a more global perspective — that is, I couldn’t exactly write European-American, African-American, etc, because I have readers from other countries. These ethnicities also mean something very different depending on where you live. This led to confusion in almost ten respondents, many of whom were white but not all, who just put in the “other” section that they were white/black/mixed race/etc.

Two last questions in this section were about the respondent’s education and vocation. Here is what I got.

A full third of respondents have PhDs. Damn, people. But I was pleased to see at least a handful of folks that were still in college (and I hope desperately that they aren’t just my current semester of students!).

So… I guess I and my doppelgangers read my blog. This demonstrates a few important things:

  • People read people who are like them.
  • If you want people who are not like you to read your blog, you probably have to step out of your comfort zone.

This is significant for a number of reasons. More prominent women sciencebloggers, for instance, likely means more female readers. Same goes with more sciencebloggers of color, of different sexualities, different physical capabilities, different countries, different ages. And since sciencebloggers can draw people into science, can excite them, inspire them to stay when they are feeling scared, and otherwise mentor them, having broader representation in scienceblogging is a Very Good Thing.

Conversely, if I want to reach something other than the white-female-straight-middle-class-academic audience, I need to be doing something different than what I’m doing right now. Some of that lies in promotion and marketing, but more of that likely has to do with voice, style and content.

What do you want from me?

Most of this section of the survey was freeform response, but I did have a few graphable questions.

What I find interesting here is that readers mostly want to read about the life of a scientist stuff (there are many women sciencebloggers who do this more regularly and eloquently than me), and more plain-old anthropology. Ladybusiness, reproductive choice, women’s reproduction, not nearly so much.

On the one hand, I think I would like to expand my writing a bit to try to write posts that have an anthropological perspective and broad appeal. On the other, if ladybusiness isn’t your top priority, readers, you don’t know what you’re missing!

I’d like to think that’s what I demonstrated last week with my iron-deficiency anemia post. If I weren’t scrabbling for tenure I could probably write a post a week on anthropological perspectives on women’s health like that post. Men and women commented on, and wrote on, that post. It made it to reddit, a few great feminism blogs, and lots of other non-science individual bloggers and livejournalers.

So ladybusiness is here to stay, but I am going to try to expand my reach. Anthropology is a discipline most don’t get in high school, so most people know next to nothing about it. It would be a great thing if I could expose more people to how cool the field can be.

What you had to say

I had two open-response questions, one on how I could attract more laypeople, and another that was just open for questions and comments. For the first question, you said:

  • Explain more terms, go for a less scholarly tone.
  • Many of you found me through Twitter, so continue using that medium.
  • Try for less of a wall of text (break it up, use pictures, etc).
  • Use more keywords so they get Googled.
  • Write “basics” posts that can be referred to again and again by laypeople, teachers and students.
  • Use surveys and other interactive widgets.

For the second, mostly you just said really nice things. Several women in academic positions more junior than me said they read me to stick with academia. I wanted to share just one quote, because it demonstrates what I’m aiming for, even if I don’t really think I’m there yet (but thank you!):

“…I really enjoy [your blog], and thank you for being one of the voices that makes ongoing work in science into something I feel I can read and follow, rather than some impenetrable ivory tower only accessible through poor mainstream media interpretation. (Even laypeople get tired of saying “They did a study! You know, the ‘they’ that ‘does studies,’ whoever ‘they’ are.”) The perspective on women’s issues is a particular bonus as well.”

I think those of us who want to write for a broader audience, if we can inspire this feeling in our readers, even some of the time, we’re doing well.

And finally, what I want from you

I didn’t write this post to inspire a conversation just about why you read my blog: I don’t need more of a lovefest and feel a little like I’ve reached Internet Saturation anyway! But I’d like to know:

  • Why do you come here?
  • Why do you read any science blog?
  • How do you think we can get your friends to read us too?

If we could inspire people to reach for other connections, with material and people they don’t know, instead of the zone of comfort they do know, it would be a marvelous thing.

An embarrassment of riches

I have been quite the fancypants lately. In addition to the flood of new traffic from Science Online 2011, and in particular my post on the women scienceblogging panel, folks have been heading here to talk about broader issues of underrepresentation and racism, and, of course, iron-deficiency and the ladybusiness.

Then, because of a happy accident and the fact that Laura Weisskopf Bleill of Chambanamoms.com wanted to help me promote some focus groups I am running for a study on doctor-patient relationships around hormonal contraceptives,* I became a Chambana Mom to Know. At the same time I was recruited by the ever-clever John Hawks to do a bloggingheads.tv diavlog where we discuss women in science, blogging in academia, my fieldwork, the ladybusiness, #aaafail, and lots of other stuff.

I am feeling quite overwhelmed by the fact that I have a lot of new readers, and this is no longer the intimate space it once was (usually when I write, I imagine myself to be talking to a group of female friends while we sit on the couch and hang out – it now feels like giving a seminar to a medium-sized room full of people, where we are somehow still able to manage cool sidebar conversations). This is new and exciting, and while there is a part of me that will grieve for that little space where I knew most of the people who read me, I am delighted to bring anthropology to more people and keep pushing myself to write more accessibly for more people.

So, I am trying to think of next steps in terms of my writing. I still owe you all a summary of the survey I did on my readers a few weeks ago: given my day job commitments, that is the plan for what will probably be my single big post of the week.

However, I also want to continue to do two things: shorter researchblogging posts on articles I find interesting, and longer posts on specific issues around women’s health, anthropology and medicine. So if there are particular papers you want me to read, particular topics you want me to cover… say so in the comments!

*I need to double-check with the IRB about whether I have approval to advertise this on the blog. If it turns out I do, expect a post on it this week!

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