Kate Clancy, PhD

Friday, May 31st 2013

Feedback Loops: The Biology and Culture of Premenstrual Experience

I think my umbilical hernia is getting bigger. I’ve had it since my pregnancy over five years ago, the result of diastasis, a situation where the abdominal muscles pull apart from the baby taking up so much darn room. I’ve consulted with a surgeon, and the hernia is tiny, not worth fixing until I’m done childbearing since having another kid would likely open it up again.

But despite a medical professional’s blessing and my own research, I’m staring at this hernia. I think it’s bigger. Or maybe I’m just bloated. Maybe I’m lactose intolerant. Or I ate something contaminated with gluten. Maybe I’m experiencing strangulation of my intestines, right now, and I should be calling the doctor or going to the ER. How long do I have? Could I pass out before getting there? Will my intestines rupture? What if they have to do surgery on me?

How many weeks will I have to stay off my skates?

My brain does this most premenstrual phases over the last year. For three to four days I become a semi-depressed hypochondriac. Because I now recognize that these thoughts increase premenstrually, I’m able to laugh about it a bit, and I’m able to set them aside by telling myself that if I feel the same way in a week, I’ll go to the doctor.

I haven’t needed to go to the doctor.

I don’t know why my premenstrual experience is like this, not exactly. It seems to be context-dependent, because it relates to one of my big fears – getting sick in a way that could derail my busy lifestyle, keep me from doing my job, make me neglect my child, or force me from my sport.

To me, being sick means letting other people down.

 

Culture- and experience-bound illness

Our illnesses, worries and feelings are all culture- and experience-bound. But alongside illnesses that appear only in certain contexts are very real, physiological phenomena that are influenced by both biology and culture. The two are not mutually exclusive.

I was motivated to write this post because Amanda Marcotte, someone I greatly admire, wrote a piece earlier this week about premenstrual syndrome (PMS) as a culture-bound syndrome. There, Marcotte points to work suggesting that the origin of PMS is in our culture, not our biology, even adding that PMS “panders” to the idea that women are overemotional. She quotes from researchers who discuss women who are “highly resistant” to evidence that PMS is culturally bound, who find PMS “convenient” as an excuse for bad behavior in order to hold on to notions of themselves as good women.

PMS is surely a culture-bound syndrome. However, Marcotte seems to imply that PMS’s cultural origin negates the possibility of there also being a biological or physiological component to PMS, and this is not the case. The definition of a culture-bound syndrome is a cluster of symptoms that appears different among different cultures. The symptoms being bounded by different cultural expectations of how they should manifest doesn’t mean there couldn’t, in some cases, be a biological component as well. There are many physical phenomena that we experience differently based on our culture, but that doesn’t mean the underlying issue isn’t real. Even the way a person responds to a stubbed toe is going to be highly dependent on that culture’s perception of pain, machismo, and a host of other culture- and gender-bound expectations.

We all still stub our toes.

 

PMS is not universal, but…

All people who have menstrual cycles have a premenstrual phase and thus premenstrual experiences. For some of those people, you can’t identify a difference between the experiences of the premenstrual phase from any other time in her cycle. For others, there is a cluster of symptoms linked to that time period. The biggest problem about the way in which PMS is embedded in our culture, to my mind, is the way it’s situated as a universal and universally negative. The only aspect of premenstrual experience that should be explicitly pathologized is anything that disrupts normal functioning. This is why we have the additional classification of premenstrual dysphoric disorder, or PMDD. Using the criteria of PMDD only 8-10% of reproductively-aged women fall into this category.

As it turns out, there is an enormous literature on the hormonal factors that may explain PMDD. And some of it may even shed light on why there is cultural variation in premenstrual experiences that make it seem as though western women overexpress negative symptoms.

One of the main mechanisms of PMDD is related to progesterone withdrawal. Mouse study after mouse study has shown that if you give a mouse a ton of progesterone, then wait a little bit, that withdrawal period is a time when the mice become depressed. If you hold them up by their tail, they don’t struggle. If you try to get them to swim, they give up (don’t worry, that doesn’t mean they drown, only float). The mechanism is related to the way in which the withdrawal of progesterone (and thus its neuroactive metabolite allopregnanolone) influences GABA receptors in the brain.

Now, all ovulatory cycles should have a midluteal (that’s about three quarters of the way through a menstrual cycle) peak of progesterone, followed by progesterone withdrawal. But not all ovulatory cycles lead to those women experiencing PMDD. What is explaining this variation in experience?

There is growing evidence that women have varying sensitivity to the hormones they produce, such that two could have the same hormone concentrations but one could have a more acute experience from progesterone withdrawal. But the other important factor here, is that because we have a lifestyle that leads to eating more and being less active than most, western, industrialized women have the highest progesterone of all women globally.

So rather than seeing this cultural variation as entirely a product of the culture-bound syndrome, we can also see that it has to do with the ways in which western women are at the farthest end of the spectrum in terms of actual hormone concentrations. We have the highest hormones, so we have the furthest to fall. Our experience of progesterone withdrawal is more frequent and more extreme than probably any other human population on the planet.

 

Biocultural approaches to the premenstrual experience

Therefore, there is both a cultural and biological component to the premenstrual experience that makes western women more likely to experience clusters of negative symptoms during this phase. I think it’s worth noticing the many important feminist contributions to our understanding of PMS and premenstrual experiences. These critiques of cultural norms that limit women’s expression have done a good job making sure that medicine better bounds the definition of PMDD, rather than pathologize all women.

At the same time, these cultural constructions need to be viewed alongside the equally important evidence that the frequent cycles and steep progesterone withdrawal produced by our energy surplus environment, individual variation in sensitivity, and individual variation in other important contexts are going to lead to diverse experiences of the premenstrual phase. Because these symptoms (positive and negative) can manifest so differently for different women, it makes sense that meta-analyses like the one Marcotte cites did not find a relationship between the premenstrual phase and low mood.

Western women live in a culture that promotes overwork; Emily Martin has pointed out that experiences of PMS may be a result of women chafing against flaws in our culture, rather than PMS representing a flaw in our bodies (1980). And so again we can see not that culture and biology are disparate, but that they can influence each other: overwork can contribute to consumption of energy-dense food and low physical activity, which drives progesterone concentrations up, which makes that withdrawal curve so steep.

In the end, it doesn’t make sense to view the biology and culture of premenstrual experiences separately. Biology and culture aren’t two sides of a coin, but the two massive and overlapping components of the feedback loop that helps us understand human motivations, behaviors, and physiology.

 

References

Martin E. 1980. The Woman in the Body: A Cultural Analysis of Reproduction. Boston: Beacon Press.

 

Addendum (6/1/13, 10pm CST)

I realized I should have provided some citations for the relationship between progesterone and mood. Here are a handful of papers that folks may find interesting:

Beckley, E. H. and D. A. Finn (2007). “Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility.” Pharmacology, Biochemistry and Behavior 87: 412-419.

Brinton, R. D., R. F. Thompson, et al. (2008). “Progesterone receptors: Form and function in brain.” Frontiers in Neuroendocrinology 29(2): 313-339.

Dantzer, R. and K. W. Kelley (2007). “Twenty years of research on cytokine-induced sickness behavior.” Brain, Behavior, and Immunity 21(2): 153-160.

Espallergues, J., L. Givalois, et al. (2009). “The 3[beta]-hydroxysteroid dehydrogenase inhibitor trilostane shows antidepressant properties in mice.” Psychoneuroendocrinology 34(5): 644-659.

Frye, C. A., A. A. Walf, et al. (2004). “Progesterone enhances motor, anxiolytic, analgesic, and antidepressive behavior of wild-type mice, but not those deficient in type 1 5[alpha]-reductase.” Brain Research 1004(1-2): 116-124.

Reed, S. C., F. R. Levin, et al. (2008). “Changes in mood, cognitive performance and appetite in the late luteal and follicular phases of the menstrual cycle in women with and without PMDD (premenstrual dysphoric disorder).” Hormones and Behavior 54(1): 185-193.

Sulak, P. J., R. D. Scow, et al. (2000). “Hormone Withdrawal Symptoms in Oral Contraceptive Users.” Obstetrics & Gynecology 95(2): 261-266.

Thursday, May 30th 2013

Ladybusiness Link Love

A new post coming shortly, but in the meantime read these other posts. A rather specific set of links this time, because there has been some pretty good ladybusiness writing in the last month.

“Why do women try to get ahead by pulling men down?” On escalators, elevators, and running as hard as you can.

Why do men keep putting me in the girlfriend zone? A great piece playing around with the “why do girls put me in the friend zone” Nice Guy trope.

‘We have always fought:’ Challenging the ‘Women, Cattle and Slaves’ narrative. On writing women and realizing the many spaces they occupy, and the stereotypes that limit our awareness of this.

Evolution, sexism and racism: why definitions matter. A succinct, thoughtful post.

24 Lies People Like to Tell Women. Because you should read it.

Women are bitches. Oh, this piece is just so lovely. On the way men talk about women, and what this reveals about what they think of them.

Cultural sexism: What if Amanda Knox had been Andrew Knox? Barbara King’s great piece on the way we think about sexuality and gender.

Exclusive: meet the woman who kicked off Anonymous’s anti-rape operations. Justice for Rehtaeh.

Elaine Morgan and the Aquatic Ape. I really enjoyed this. It’s important to remember the contributions Morgan made to try and subvert some of the sexism of her time, even though aquatic ape will never be supported by evidence. Margie Profet’s hypothesis on sperm-borne pathogens driving evolution of menstrual will also never be supported, and yet the way she pushed against the “women are dirty” cultural conditioning was important for the field. Sometimes scholarly contributions are less about whether their prime mover hypothesis is right, and more about what it forces us to confront about our biases.

Tuesday, May 21st 2013

Your Lady Parts Don’t Like It When You Get Sick: Relationships Between Immune Health and Reproductive Hormones

Life history trade-offs are the bread and butter of biological anthropology. The way we understand the importance of certain traits and life events is in how they vary in response to selection pressures like energy availability or climate, but also cultural beliefs and practices.

That’s why it matters to us when you got your first period, or what your birth weight was, or how closely you decided to space your children, or if you had them at all. And we will delightedly explain the different selection pressures that push and pull on these events and traits, like how the travel soccer team you were so serious about as a kid might have delayed puberty for you just a little, but how that’s great because later puberty can lead to a lower lifetime hormone exposure and a lower risk for reproductive cancers.

We’re really fun at parties.

The broader importance of understanding all this variation, for the folks who aren’t nerding out on human evolution, is that it demonstrates that, well, we’re variable. And variable is normal, generally not worrisome or pathological. So studying variation directly contradicts a normative perspective that can make one feel like there’s only one way to be female, or one way to be male. I also think it can make us feel powerful, like we have strong, good bodies that are responsive to environmental variables and make smart somatic decisions.

One of the trade-offs I’ve grown increasingly interested in is the one between maintenance – that’s the effort you make keeping up the basic functions of your body, like digestion, circulation, but also immune function – and reproduction. Certain stressors can force the body to allocate more towards maintenance, which leaves fewer energetic resources for reproduction. For instance, if you are exposed to the cold virus, and you get a cold, your immune system is going to have to expend some additional energy fighting it off. This energy could have gone towards boosting your reproductive hormones just a little bit, or making your endometrium plush for the possibility of a baby.

Another way we’re fun at parties

Like many anthropologists in human biology, I have a freezer full of other people’s spit and pee from past projects. In my case the samples are from rural Polish women during the harvest season, over a menstrual cycle. In the past I’ve assayed all of it for reproductive hormones (estradiol and progesterone) and C-peptide (a biomarker of energy availability). But they have been waiting, preserved in the event a new laboratory methodology allows us to ask new questions.

My former student, Laura Klein (now a PhD student at Harvard) was able to use some old methodologies on measuring C-reactive protein in rat urine and tweak it to apply it to humans. C-reactive protein (CRP) is considered a measure of systemic inflammation, to some even a broad indicator of maintenance effort. So of course we decided to crack open the spit-and-pee freezer and pull out the Polish urine samples, because measuring CRP in these women alongside their reproductive hormones could tell us about maintenance versus reproduction trade-offs.

What we found

In this population of rural, agricultural women, CRP was negatively associated with progesterone – so the higher an individual’s CRP, the lower her progesterone (Figure 1). Progesterone is the hormone that is higher in the second half of the cycle. It is produced by the corpus luteum, which is what is left behind by the follicle that ovulates. Progesterone maintains the endometrium’s thickness and supports early pregnancy, and this latter-half functioning of the cycle tends to be the first that has energetic resources allocated away from it in the event some other part of the body needs it.

There was a similar association with estradiol and CRP through the menstrual cycle, but it was not statistically significant, suggesting the relationship is not large or meaningful, at least in this sample. However, when we added age at menarche (first period) as a variable in our statistical models, age at menarche and CRP together seemed to influence estradiol. And the relationship between menarcheal age and CRP was interesting too: women who had gotten their first periods when younger had higher CRP.

We have some reason to suspect that this measure of CRP can tell us something about immune challenges. CRP breaks down into monomeric subunits when it gets to where it’s needed to help orchestrate the inflammatory process. Because we measured CRP from urine, only the monomeric subunits can be measured (the larger pentameric CRP, what’s normally measured in serum, can’t get through the kidneys). So we’re measuring the pro-inflammatory phenotype of what is left behind when a body needs to take care of inflammation.

Punchline

These associations are making us think that there is a lot more to adult ovarian hormones and fertility than we had first thought. Immune health and the childhood environment are both proving to be important to adult functioning. In future work, we really want to look at the immune environment during childhood to see if better measures of immune environment like microbial exposure from farm animals or history of illness and diarrheal episodes will help us understand what is driving this inflammation/reproduction relationship.

 

The paper: Clancy KBH, Klein LD, Ziomkiewicz A, Nenko I, Jasienska G, Bribiescas RG (2013). Relationships between biomarkers of inflammation, ovarian steroids, and age at menarche in a rural Polish sample. American Journal of Human Biology.25(3): 389-398.