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.
Figure 1. Women with high CRP (black squares) have lower progesterone through the luteal phase than women with low CRP (white squares).
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.
