I worked on this project for all of 2020. It feels great to have the paper out in an open access journal so people who are keen can check it out. The paper is about how endometriosis and PCOS, the two most common female reproductive conditions, are related to one another.
The idea for the project began a few years ago when I was learning about the role of oxytocin in endometriosis. Women with endometriosis tend to have higher levels of oxytocin in their blood and uterus, which appears to increase the contractility of the uterine musculature. This can play a role in the disease, as more forceful contractions create pain as well as possibly increase the quantity of retrograde menstruation (when menstrual blood goes back into the body rather than out of it).
During this initial investigation, I found a tiny bit of evidence suggesting that women with PCOS may have uteri that are less contractile, indicating that these women could have less oxytocin. After my 2017 project was published, someone did report finding lower serum oxytocin in women with PCOS.
My professor has developed an evolutionarily-minded way of studying disease over the past decade and a half: it's called 'diametric disorders'. Diametric means opposite. This way of examining disease involves investigating a given biological system - it could be a gene, a hormone, a network in the brain, a psychological adaptation, or something else.
Put simply, biological systems can develop and express toward relatively less or more activity. A simple example is the immune system: an under-active immune system makes you more susceptible to infection while an over-active immune system can engender autoimmune conditions like rheumatoid arthritis.
Pairs of diseases that manifest from reduced or elevated activity of the same biological system will manifest with opposite symptoms. We began to suspect that this was the case with endometriosis and PCOS, so I spent all of 2020 exploring this question.
We learned that, in contrast to PCOS which centrally involves high levels of testosterone (including high testosterone exposure in utero), endometriosis appears to involve low levels of testosterone. This is an over-simplification, but you can read the details in the publication, of course.
Testosterone exposure has important impacts on the developing fetus, whether they are male or female. Female fetuses are usually exposed to much lower levels of testosterone than male fetuses, but variation is high. Maternal stress, age, metabolism, and genetics all play a role in how much testosterone the fetus receives .
When females are exposed to high levels of testosterone, PCOS can develop. The ovaries produce high levels of testosterone and the brain continues to send a hormonal signal to tell the ovaries to continue doing so.
We compiled evidence to suggest that opposite dynamics are at play in endometriosis. Research has largely focused on how high levels of estrogen (estradiol in particular) play a role in the inflammatory and proliferative nature of endometriosis, but our review points to an important role of testosterone, and an important role of the balance of estrogen and testosterone.
This project also reveals how female reproductive traits, such as onset of puberty, menopause, ovarian aging, ovulation, and secondary sex characteristics, are constellated together within individuals. We can learn about patterns of selection as well as tradeoffs between traits that help us survive and traits that help us mate successfully through exploring these two reproductive conditions.
So our way of looking at these conditions is seeing them as extreme expressions of testosterone-mediated female development.
A future project will examine how sexual selection by males on females contributes to these diseases.